Constituent concentration measuring apparatus and constituent concentration measuring apparatus controlling method

ABSTRACT

An object of the present invention is to provide a noninvasive constituent concentration measuring apparatus and constituent concentration measuring apparatus controlling method, in which accurate measurement can be performed by superimposing two photoacoustic signals having the same frequency and reverse phases to nullify the effect from the other constituent occupying large part of the object to be measured. The constituent concentration measuring apparatus according to the invention includes light generating means for generating two light beams having different wavelengths, modulation means for electrically intensity-modulating each of the two light beams having different wavelengths using signals having the same frequency and reverse phases, light outgoing means for outputting the two intensity-modulated light beams having different wavelengths toward a test subject, and acoustic wave detection means for detecting an acoustic wave generated in the test subject by the outputted light.

TECHNICAL FIELD

The present invention relates to a noninvasive constituent concentrationmeasuring apparatus and constituent concentration measuring apparatuscontrolling method, particularly to the noninvasive apparatus and methodin which glucose of a blood constituent is set as a measuring object tomeasure a concentration of the glucose, i.e., a blood sugar level in anoninvasive manner.

BACKGROUND ART

Various methods are proposed to date as the noninvasive constituentconcentration measuring method based on percutaneous irradiation ofelectromagnetic wave and/or observation of radiation. In these methods,an interaction between the objective blood constituent, for example, aglucose molecule in the case of a blood sugar level, and theelectromagnetic waves having a particular wavelength, i.e., absorptionor scattering is utilized.

However, the interaction between the glucose and the electromagneticwave is weak, there is a limitation to intensity of the electromagneticwave with which a living body can safely be irradiated, and the livingbody is a scatterer for the electromagnetic wave. Therefore,satisfactory result is not obtained so far in the blood sugar levelmeasurement of the living body.

An photoacoustic method of irradiating the living body with theelectromagnetic wave to observe an acoustic wave generated in the livingbody deserves attention among the conventional techniques of utilizingthe interaction between the glucose and the electromagnetic wave.

The photoacoustic method is a method of measuring an amount of moleculein the living body by measuring pressure of the acoustic wave. That is,when the living body is irradiated with a certain amount ofelectromagnetic wave, the electromagnetic wave is absorbed in themolecule contained in the living body, the acoustic wave is generated bya local heating of the region irradiated with the electromagnetic wavefollowed by thermal expansion, and the pressure of the acoustic wavedepends on the amount of molecule absorbing the electromagnetic wave.Furthermore among the photoacoustic method, a method in which heat isgenerated in a local area irradiated with the light, and the thermalexpansion occurs locally without thermal diffusion to generate thepropagating and finally utilized acoustic wave, is called the directphotoacoustic method.

The acoustic wave is a pressure wave propagating in the living body, andthe acoustic wave has a feature that it is less prone to scatteringeffect as compared with the electromagnetic wave. Therefore, thephotoacoustic method is a noteworthy technique in the blood constituentmeasurement of the living body.

FIGS. 49 and 50 show, configuration examples of the prior art forconstituent concentration measuring apparatus in which the photoacousticmethod is utilized.

FIG. 49 shows an example for the first prior art example in which alight pulse is used as the electromagnetic wave (for example, seeNon-Patent Document 1). In this example, blood sugar, i.e., glucose isset as a measuring object in the blood constituent. In FIG. 49, a drivepower supply 604 supplies a pulse-shaped excitation current to a pulselight source 616, the pulse light source 616 generates a light pulsehaving a duration of sub-microsecond, and a living body test region 610is irradiated with the light pulse. The light pulse generates thepulse-shaped acoustic wave called a photoacoustic signal in the livingbody test region 610, and an ultrasonic detector 613 detects thephotoacoustic signal to convert it into an electric signal proportionalto the acoustic pressure.

A waveform of the electric signal is observed by a waveform observingapparatus 620. Since the apparatus 620 is triggered by a signalsynchronized with the excitation current, the electric signalproportional to the acoustic pressure is displayed at a predeterminedposition on a screen of the waveform observing apparatus 620, and thesignals can be integrated and averaged.

Amplitude of the obtained electric signal proportional to the acousticpressure is analyzed to measure the amount of blood sugar level, i.e.,the amount of glucose in the living body test region 610. In the exampleshown in FIG. 49, the sub-microsecond light pulses are generated in arepetition up to 1 kHz, averaged measurement for 1024 light pulsesprovides the electric signal proportional to the acoustic pressure.However, the sufficient accuracy is not obtained.

Therefore, an example of the second prior art in which a continuouslyintensity-modulated light source is used is disclosed to increase theaccuracy. FIG. 50 shows a configuration of an apparatus of the secondconventional example (for example, see Patent Document 1). In thisexample, the blood sugar is set as the main measuring object, andmultiple light sources having different wavelengths are used to attempta measurement with the high accuracy.

To avoid explanation from becoming complicated, the operation with thetwo light sources will be exemplified with reference to FIG. 50. In FIG.50, the light sources having the different wavelengths, i.e., a firstlight source 601 and a second light source 605 are driven to emitcontinuous light beams by a drive power supply 604 and a drive powersupply 608 respectively.

The light beams output from the first light source 601 and the secondlight source 605 are modulated by a chopper plate 617 which is driven bya motor 618 and rotated at the constant number of revolutions. Thechopper plate 617 is made of an opaque material, a shaft of the motor618 is positioned at the center of concentric circles, of whichcircumferences where the light beams of the first light source 601 andthe second light source 605 pass respectively have mutually-indivisiblenumbers of apertures.

The light beams output from the first light source 601 and the secondlight source 605 are intensity-modulated by a mutually indivisiblemodulation frequency f₁ and a modulation frequency f₂, the light beamsare combined by a coupler 609, and the living body test region 610 isirradiated by the combined light beam.

In the living body test region 610, the photoacoustic signal having thefrequency f₁ is generated by the light of the first light source 601,and the photoacoustic signal having the frequency f₂ is generated by thelight of the second light source 605. The photoacoustic signals aredetected by an acoustic sensor 619 and converted into the electricsignals proportional to the acoustic pressures, and frequency spectrumis observed by a frequency analyzer 621.

In the example, all the wavelengths of the multiple light sources areset at absorption wavelengths of glucose, and photoacoustic signalintensity at each wavelength is measured as the electric signalcorresponding to the amount of glucose contained in the blood.

In this configuration, a relationship between the measured intensity ofthe photoacoustic signal and the glucose concentration measured from theseparately collected blood are previously stored to measure the glucoseamount from the observed value of the photoacoustic signal.

On the other hand, in health management and treatment, it is importantto continuously perform the measurement while the constituentconcentration measuring apparatus is carried around. Therefore, aportable type or wearable constituent concentration measuring apparatusis also developed. The following examples for the third and fourth priorarts are disclosed as the portable type constituent concentrationmeasuring apparatus.

The third example shown in FIG. 51 is an example mounted on a eyeglasseshandle that comes into contact with the back of an ear (for example, seePatent Document 2). In FIG. 51, both a light source 500 and an acousticwave detector 541 are embedded in a contact surface of an apparatus body540 with a living body 499. In the acoustic wave generated in the livingbody 499 by the irradiation light emitted from the light source 500, apart of the acoustic wave propagating backward is detected by theacoustic wave detector 541.

The fourth example shown in FIG. 52 is an example mounted on an erring(for example, see Patent Document 2). In FIG. 52, the apparatus body 540comes into contact with the living body 499 from both sides, the lightsource 500 is embedded in one of the contact surfaces of the apparatusbody 540, and the acoustic wave detector 541 is embedded in the othercontact surface. In the acoustic wave generated in the living body 499by the irradiated light emitted from the light source 500, a part of theacoustic wave propagating forward is detected by the acoustic wavedetector 541.

-   [Patent Document 1] Japanese Patent Application Laid-Open (JP-A) No.    10-189-   [Patent Document 2] JP-A No. 8-224228-   [Non-Patent Document 1] Thesis (University of Oulu, Finland) “Pulse    photoacoustic techniques and glucose determination in human blood    and tissue”, (IBS951-42-6690-0,    http://herkules.oulu.fi/isbn9514266900/, 2002)

DISCLOSURE OF THE INVENTION Problem to be Solved by the Invention

In the above examples, there are the following problems. In the firstprior art, because the measurement is repeated using the pulse lightsource, there is a problem that a long time is required to perform themeasurement.

About two-thirds of a human body or an animal body is made of water, andwater occupies near 80% in the blood constituent, while a water moleculeexhibits significant absorption of lights having wavelength longer than1 μm. On the other hand, a glucose molecule exhibits the absorptioncharacteristics in the light wavelength bands near 1.6 μm and 2.1 μm. Ina concentration ranging from 50 to 100 mg/dl (2.8 to 5.6 mM) which isthe blood sugar level of a healthy subject, water has the absorption1000 times larger than glucose. Accordingly, in order to measure theblood sugar level, it is necessary that the measurement is performedwith an accuracy higher than 0.1%. Usually the accuracy of 5 mg/dl (0.28mM) is required for the blood sugar level measurement, so the necessaryaccuracy is estimated to be ca. 0.003%. Thus, the extremely highmeasurement accuracy is required in order to measure the bloodconstituent concentration, particularly in order to measure the bloodsugar level, i.e., the glucose amount.

In the above prior art, when other constituents in the blood or theconstituent in a non-blood tissue also exhibits the absorption in thewavelength in which the objective blood constituent exhibits absorption,in the generated photoacoustic signal, the other blood constituents orthe constituent in a non-blood tissue also constibute. Since thephotoacoustic signal which might be generated in a non-blood tissue, isalso added, measurement is highly prone to the ambient disturbances.Accordingly, in order to measure the blood constituent with higheraccuracy, the photoacoustic signal generated in the blood needs to beseparated from the other photoacoustic signals.

When the higher accuracy is to be achieved by repeating and averagingthe signals by the pulse light source, the necessary number ofmeasurements must be increased, which lengthens a measuring time. Forexample, even if the signal is obtained with accuracy of 1% per pulseusing the pulse light source, it is necessary to measure for 110,000pulses in order to improve the accuracy up to 0.003% by averaging. Inthe case where the pulse light source has a repetition of 1 kHz, 110seconds are required for the measurement.

During the blood sugar level measurement, it is necessary that a subjectis kept motionless, which imposes physical stress to the subject. In thecase where a test subject is an animal, it is extremely difficult tokeep the animal motionless for a long time. In the photoacoustic methodmeasurement, the living body test region 610 is irradiated with thelight to generate the acoustic wave, and the acoustic wave propagatingin the living body is detected by the ultrasonic detector 613 shown inFIG. 49 or the acoustic sensor 619 shown in FIG. 50. The ultrasonicdetector 613 and the acoustic sensor 619 are in contact with the livingbody test region 610. In order to improve acoustic wave measuringefficiency, it is necessary to apply a gel containing a large amount ofmoisture to the contact surface between a skin of the living body testregion 610 and the ultrasonic detector 613 or the acoustic sensor 619 toestablish a good acoustic coupling. In this case, fine air bubblesevaporated from the living body test region 610 are mixed in the gel toresult in an error.

When a change in relative position happens between the detector such asthe ultrasonic detector 613 or the acoustic sensor 619 and the livingbody test region 610, the acoustic coupling is influenced. Therefore, itis necessary for the subject to be motionless during the measurement.

The acoustic pressure measured by the ultrasonic detector 613 or theacoustic sensor 619 is reversely proportional to a distance between thedetection portion where the ultrasonic detector 613 or the acousticsensor 619 comes into contact and the irradiation portion where theliving body test region 610 is irradiated by the light. However, thedistance between the detection portion and the irradiation portion iseasily changed depending on how the ultrasonic detector 613 or theacoustic sensor 619 is pressed against the living body test region 610.Accordingly, in order to keep the distance between the detection portionand the irradiation portion constant, it is necessary that the livingbody test region is contacted with the ultrasonic detector 613 or theacoustic sensor 619 at a constant pressure and without relative motionas well.

As described later, the photoacoustic signal of the living body testregion 610 is dependent on specific heat, thermal expansion coefficient,sound velocity, and the like. The specific heat, the thermal expansioncoefficient, and the sound velocity are quantities which are changeableby a temperature (body temperature), and above all the thermal expansioncoefficient is as sensitive as about 3%/° C. The sound velocity is alsochanged by the frequency of the acoustic wave, and it is also reportedthat all of the specific heat, the thermal expansion coefficient, andthe sound velocity are changed depending on the blood sugar levelitself.

Therefore, in the first prior art, it is necessary to measure at leastthe body temperature to correct the measured value of the photoacousticsignal. Compilation of high-accuracy basic data for the correction isnot an easy task. Even if such correction data is successfullycollected, it takes a long time to verify the reliability of the bloodsugar calculated using such complicated correction.

On the other hand, in the second prior art, since the photoacousticsignals for the multiple different wavelengths are simultaneouslymeasured, there is a possibility that all of the changeable factors,such as the acoustic coupling condition, the distance between thedetection portion and the irradiation portion, the specific heat, thethermal expansion coefficient, and the sound velocity are eliminated asan unknown multiplier.

That is, in the case where absorption coefficients α₁ ^((b)) and α₂^((b)) of the background (water) for the light beams having a wavelengthλ₁ and a wavelength λ₂ and molar absorption coefficients α₁ ⁽⁰⁾ and α₂⁽⁰⁾ of the objective blood constituent (glucose) are already known,simultaneous equations for measured values S₁ and S₂ of thephotoacoustic signal for the wavelengths are expressed as follows:C(α₁ ^((b)) +Mα ₁ ⁽⁰⁾)=s ₁  [Formula 1]C(α₂ ^((b)) +Mα ₂ ⁽⁰⁾)=s ₂The formula (1) is solved to compute an unknown blood constituentconcentration (blood sugar level) M where C is an unknown multipliercontaining the above changeable factors.

M can be computed from the formula (1) even if C is unknown. At thispoint, in the case where the measurements with third and fourthwavelengths are added, the number of equations becomes excessive ascompared with the number of unknown numbers. However, even in this case,it is known that M is obtained as the best solution in the sense of theleast-square method.

However, the photoacoustic signal is not exactly linear to theabsorption coefficient. As a result, the unknown multipliers C are notequal to one another between measurements for the wavelength λ₁ andwavelength λ₂ experiencing different absorption coefficients of thewater.

In the second prior art, the photoacoustic signal depends also on amodulation frequency f. Accordingly, the unknown multipliers C are notequal in the photoacoustic signals generated in the different modulationfrequencies.

Thus, because C in the first line differs from C in the second line inthe formula (1), usually it is impossible to solve the formula (1) todetermine M. When a functional form of the unknown multipliers C for theabsorption coefficient α, and the modulation frequency f is completelydetermined, the formula (1) would possibly be solved. However, asdescribed later, it is found that the functional form itself is possiblychanged by the amount of scattering.

In the second prior art, because the photoacoustic signal is not exactlylinear to the absorption coefficient, it is necessary to perform thecomplicated correction to the measurements for the wavelength λ₁ andwavelength λ₂ experiencing different absorption coefficients of thewater.

In the second prior art, the photoacoustic signal also depends on themodulation frequency f. Accordingly, it is necessary to perform the evenmore complicated correction to the measured values of the photoacousticsignals generated for the different modulation frequencies.

In the second conventional example, there is also the problem arisingfrom uneven frequency characteristics of the acoustic sensor 619 betweenthe frequencies f₁ and f₂.

The unevenness of the frequency characteristics also results from thefollowing cause. The acoustic wave is reflected unavoidably by acousticimpedance mismatch at the boundary between the examined region of theliving body and a surrounding substance (air in this case). As a result,the detected photoacoustic signal is influenced by the boundaryreflection according to the shape of the living body test region, andthe frequency of a standing wave of the photoacoustic signal varies, sothat it is difficult that the constituent concentration is computed fromthe detected photoacoustic signal evenly across individuals.

In the photoacoustic method, in order to obtain information on theabsorption coefficient α, it is necessary that the acoustic wavewavelength is shorter than the absorption length of about α⁻¹×2π. In aglucose molecule absorption band near a light wavelength of 1.6 μm,since the water absorption coefficient is about α=0.6 mm⁻¹, it isdesirable that the acoustic wave wavelength is 10 mm or less. At thispoint, because the sound velocity c is about 1.5 km/s in water, it isnecessary to use the modulation frequency of 150 kHz or higher.Similarly for a glucose absorption band near the light wavelength of 2.1μm, the water absorption coefficient becomes about four times of thatfor glucose, the desirable acoustic wave wavelength is 2.5 mm or less,and the desirable modulation frequency is 0.6 MHz or higher.

In a view of practicality, there is also the problem that the intensitymodulation at such a high frequency is realized using the chopper plate617 rotated by the motor as described in the second prior art. For anultrasonic wave having the wavelength of 10 mm or the wavelength 2.5 mmor less, the wavelength of the ultrasonic wave is close to a device sizeof a normally utilized ultrasonic detector. Therefore, the standing waveis easily generated and it is very difficult to realize the detectorhaving flat frequency characteristics. The detector in which resonantphenomenon is suppressed by a damper material is available, however,even in this case, unevenness of about ±2 dB still remains in thesensitivity.

If the frequency dependence of the detector sensitivity is flat, in thesecond prior art, a difference in sensitivity between the differentmodulation frequencies can be corrected. However, the frequencydependence of the detector sensitivity changes by the temperature, andthe frequency dependence of the detector sensitivity is also changed bythe contact condition between the detector and the living body. Theformer is attributable to the change in mechanical coefficient such asYoung's modulus and the size change caused by the thermal expansion, andthe latter is attributable to a fluctuation in resonant Q value (QualityFactor) due to the change in degree of the scattering of elastic energyby the contact. Accordingly, since certain means or a jig forstabilizing acoustic coupling is required in addition to a thermometer,it is very difficult to exactly correct the difference in detectorsensitivity for different modulation frequencies.

FIG. 53 shows an example of the change in Q value of the resonancecharacteristics in the photoacoustic signal detector. In FIG. 53, thephotoacoustic signal detection sensitivity characteristics indicated bya solid line is changed to the detection sensitivity characteristicsindicated by a broken line by the change in pressing force between theliving body test region and the photoacoustic signal detector. In theexample shown in FIG. 53, a peak value of the photoacoustic signaldetection sensitivity indicated by the solid line decreases almost toits half in the one indicated by the broken line.

Then, FIG. 54 shows another example of the change in frequencycharacteristics of the photoacoustic signal detector sensitivity. InFIG. 54, the detector sensitivity frequency characteristics indicated bythe solid line shows the state immediately after the living body testregion is brought into contact with the photoacoustic signal detector.That is, the photoacoustic signal detector has an ambient airtemperature of, for example, about 20° C., the living body has the bodytemperature of, for example, about 36° C., and there is a temperaturedifference of about 16° C. between these.

Then, the photoacoustic signal detector sensitivity frequencycharacteristics indicated by the broken line of FIG. 54 shows a statewhen about ten minutes have elapsed. The peak frequency is changed byabout 10 KHz across the photoacoustic signal detector sensitivityfrequency characteristics indicated by the solid line and broken line inFIG. 54.

A technique of utilizing the detector resonance characteristics toachieve the improvement of the detection sensitivity is well known (forexample, see Edited by T. Sawada, “Photoacoustic spectroscopy and itsapplication-PAS”, Japan Scientific Society Press, 1982). However, in thesecond prior art, since the measurements are performed for the multiplemodulation frequencies, it is impossible to utilize the resonancecharacteristics to improve the sensitivity.

As described above, in the noninvasive blood constituent concentrationmeasuring method shown in the first and second prior arts, there are thefollowing problems to be solved: (1) Because many parameters which arehardly kept constant exist in the measurement, the photoacoustic signalcannot be converted into the blood constituent concentration with asufficient accuracy. (2) Due to the non-linearity in respect to theabsorption coefficient and the modulation frequency dependence, even ifthe photoacoustic signal is measured for multiple wavelengths, thephotoacoustic signal values for these multiple wavelengths cannot beconverted into the blood constituent concentration by the simultaneousequations. (3) Due to the difficulty of the detector frequencycharacteristics correction, it is difficult to enhance the sensitivityfor the photoacoustic signal detection by applying resonance typedetectors. (4) The accuracy of the detected photoacoustic signal isdeteriorated due to a boundary reflection between the test subject andthe surrounding thereof, a pressure and vibration imposed to theultrasonic detection unit, and a condition on sound collection and atemperature change in the ultrasonic detection unit.

On the other hand, in the third prior art, as shown in FIG. 51, thelight source 500 and the acoustic wave detector 541 are placed in thesurface in which the apparatus body 540 is brought into contact with theliving body 499. However, the mounting state shown in FIG. 51 has thefollowing problem to be solved.

That is, as described later, in the wearable type constituentconcentration measuring apparatus of the invention, the light having awavelength longer than 1 μm is suitable for the irradiation of livingbody. However the moisture occupying the large part of living bodyexhibits the strong absorption for the light having the wavelengthlonger than 1 μm. Therefore, in the case where the living body 499 ofFIG. 51 is irradiated with the light source 500, the ultrasonic wavewhich is generated by the absorption of the glucose molecule, islocalized in the surface of the irradiated portion immediately below thelight source 500, and the ultrasonic wave is regarded as a sphericalwave. As shown in FIG. 51, it is difficult to detect the ultrasonic waveusing the acoustic wave detector 541 placed on the same surface next tothe light source 500.

In the fourth prior art shown in FIG. 52, there is the following problemto be solved. That is, in the configuration shown in FIG. 52, assumingthat r is a distance between the light source 500 and the ultrasonicdetector 541, α is a light absorption coefficient of a glucose aqueoussolution, and λ is an ultrasonic wave wavelength, it is necessary thatthe following formula (2) hold in order to measure the glucoseconcentration.r

α ⁻¹λ/(2π)  [Formula 2]

For instance, provided that the light wavelength with which the livingbody 499 is irradiated is set at the glucose absorption band of about1.6 μm, considering the water absorption coefficient is approximatelyα=0.6 mm⁻¹, it is desirable that r is 10 mm or more which issufficiently larger as compared with 2 mm, and it is also desirable thatthe wavelength λ of the ultrasonic wave is 10 mm or less.

In the case where the light wavelength with which the living body 499 isirradiated is set at the glucose absorption band of about 2.1 μm,considering the water absorption coefficient becomes about four timesthe above case, it is desirable that r is 2.5 mm or more, and it is alsodesirable that the wavelength λ of the ultrasonic wave is 2.5 mm orless.

As shown above, it is necessary that the generated ultrasonic wavewavelength λ is made shorter as compared with the distance between thelight source 500 and the ultrasonic detector 541, i.e., a thickness ofthe living body 499 which is the measurement objective.

In FIG. 52, since the living body 499 is soft, the distance between thelight source 500 and the ultrasonic detector 541 is changed according tothe force pressing the ultrasonic detector 541 against the living body499. The spherical wave of the ultrasonic wave generated immediatelybelow the light source 500 includes a portion which directly reaches theultrasonic detector 541 and a portion which reaches the ultrasonicdetector 541 after being repeatedly reflected by the boundary surfacebetween the living body 499 and air.

Because the wavelength λ of the ultrasonic wave is small compared withthe size of the living body 499, even if the distance is fixed betweenthe light source 500 and the ultrasonic detector 541, the interferencecondition between the direct wave and the multiple indirect waves whichreach the ultrasonic detector 541 changes depending on shape of theboundary between the living body and air, which affects the amount ofultrasonic wave detected by the ultrasonic detector 541.

Thus, in the fourth prior art, there is a problem that the error iscaused on the ultrasonic wave detected by the ultrasonic detector 541even if the shape of the living body 499 is slightly changed during themeasurement.

On the other hand, in the photoacoustic method, there is a followingproblem. In the photoacoustic method, the desirable frequency ofacoustic wave to detect depends on an object of the measurement. Whenthe blood in the living body is set as the measurement object, it isdesirable that the frequency of the acoustic wave to detect is theultrasonic wave near several hundreds kilohertz. However, when theultrasonic wave reaches the boundary from a medium 1 to a medium 2,there happen two phenomena. One of the phenomena is transmission acrossthe boundary. The other is the reflection on the boundary surface. Whenthe media considerably differ from each other in terms of the acousticimpedance, the large part of ultrasonic waves is reflected at theboundary surface and the transmission hardly occurs. Here, assuming thatZ₁ is the acoustic impedance of the medium 1 and Z₂ is the acousticimpedance of the medium 2, a reflectance R is expressed by the followingformula (3).

$\begin{matrix}{R = \frac{Z_{2} - Z_{1}}{Z_{2} + Z_{1}}} & \left\lbrack {{Formula}\mspace{14mu} 3} \right\rbrack\end{matrix}$

Let us consider the reflectance when a finger of a human body is set asthe test subject. FIG. 55 is a sectional view of a human finger. Asshown in FIG. 55, in the human finger, a muscle 214 exists in the centerof a bone 213, the bone 213 is surrounded by a fat 215, and thesurroundings of the fat 215 are covered with cuticle 216. Table 1 showsacoustic impedance of each of these.

TABLE 1 Sound velocity Region (m/s) Acoustic impedance Cuticle 1470 1.58Fat 1490 1.6 Muscle 1600 2.1 Bone 4000 7.8

The reflectance amounts 65% at the boundary between the bone 213 and thefat 215, when the reflectance is computed from the acoustic impedanceusing the formula (3). Therefore, the large part of acoustic wavesimpinging on the bone 213 are reflected and scattered.

FIG. 56 shows an example in which the photoacoustic signal is reflectedand scattered by the bone. FIG. 56 is a sectional view showing humanfinger, FIG. 56( a) shows how the photoacoustic signal is scattered bythe bone, and FIG. 56( b) shows how the photoacoustic signal isattenuated by the bone. As shown in FIG. 56( a), when a line extendingthe path of an excitation light 219 incident to the finger completelyhits the bone 213, the photoacoustic signal is scattered and thephotoacoustic signal can hardly be detected by a detector 220. As shownin FIG. 56( b), when the bone 213 exists near the extended path of theexcitation light 219, since a part of the photoacoustic signal isscattered, the intensity detected by the detector 220 is decreased.Thus, in the conventional photoacoustic method, there is the problemthat the photoacoustic signal intensity varies across measurements bythe influence of the reflection and scattering.

In the photoacoustic method where the acoustic wave propagating throughthe test subject is detected, it is necessary that the test subject andthe detector 220 are brought into close contact with each other. Theacoustic wave loss at the boundary surface between the test subject andthe detector 220 changes depending on the contact pressure. Thus, thereis also the problem that the photoacoustic signal intensity variesacross each measurement by the change in pressing force.

In view of the foregoing problems, an object of the invention is toprovide a noninvasive constituent concentration measuring apparatus anda constituent concentration measuring apparatus controlling method, inwhich the blood constituent concentration can accurately be measured,the high-sensitive measurement can also be performed using resonancetype detector, the measurement can be performed in a short time so asnot to place a burden on a subject, and the apparatus is compact so asto be attachable to a living body test region.

Another object of the invention is to provide a noninvasive constituentconcentration measuring apparatus and a constituent concentrationmeasuring apparatus controlling method.

Means for Solving Problem

A constituent concentration measuring apparatus according to one aspectof the present invention is characterized by comprising light generatingmeans for generating light; frequency sweep means for sweeping amodulation frequency, the light generated by the light generating meansbeing modulated in the modulation frequency; light modulation means forelectrically intensity-modulating the light using a signal from thefrequency sweep means, the light being generated by the light generatingmeans; light outgoing means for outputting the intensity-modulated lighttoward an object to be measured; acoustic wave detection means fordetecting an acoustic wave which is generated in the object to bemeasured by the outputted light; and integration means for integratingthe acoustic wave in a swept modulation frequency range, the acousticwave being detected by the acoustic wave detection means.

In one aspect of the invention, the light is electricallyintensity-modulated using the modulation signal whose frequency is sweptin a predetermined range, the object to be measured is irradiated withthe intensity-modulated light to detect the photoacoustic signal whichis an acoustic wave generated in the object to be measured by theirradiation light, and the detected photoacoustic signal is integratedto compute the constituent concentration which is the measurementobjective in the object to be measured. Thus the change in sensitivitycharacteristics of the acoustic wave detection means can be tracked tomeasure the constituent concentration which is the measurement objectiveat the frequency where the optimal sensitivity is attainable.

A constituent concentration measuring apparatus according to one aspectof the invention comprising light generating means for generating light;light modulation means for electrically intensity-modulating the lightat a constant frequency, the light being generated by the lightgenerating means; light outgoing means for outputting the intensitymodulated light toward an object to be measured, the intensity modulatedlight being intensity-modulated by the light modulation means; andacoustic wave detection means for detecting an acoustic wave which isemitted from the object to be measured irradiated with the intensitymodulated light, the constituent concentration measuring apparatuscharacterized in that an acoustic matching substance and the object tobe measured can be arranged between the light outgoing means and theacoustic wave detection means, the acoustic matching substance havingacoustic impedance substantially equal to that of the object to bemeasured.

One aspect of the invention is characterized in that the photoacousticsignal is detected under the environment whose acoustic impedance issubstantially equal to that of the object to be measured. The object tobe measured is irradiated with a light intensity modulated at a constantfrequency, the photoacoustic signal which is the acoustic wave emittedfrom the object to be measured is detected to measure the concentrationof a particular constituent contained in the liquid by the acoustic wavedetection means though the acoustic matching substance. The acousticwave detection means detects the photoacoustic signal through theacoustic matching substance, which alleviates the signal loss caused byreflection of the acoustic wave. The reflection of the photoacousticsignal is caused by a boundary reflection between the object to bemeasured and surroundings, and the reflection of the photoacousticsignal also occurs at the contact between the object to be measured andthe acoustic wave detection means. Here the object to be measured andthe acoustic matching substance having the acoustic impedancesubstantially equal to that of the object to be measured can be arrangedbetween the light outgoing means and the acoustic wave detection means.Thus reflection at the boundary between the object to be measured andthe surroundings can be decreased.

A constituent concentration measuring apparatus according to one aspectof the invention is characterized by comprising light generating meansfor generating light; light modulation means for electricallyintensity-modulating the light at a constant frequency, the light beinggenerated by the light generating means; light outgoing means foroutputting the intensity modulated light toward an object to bemeasured, the intensity modulated light being intensity-modulated by thelight modulation means; acoustic wave detection means for detecting anacoustic wave which is emitted from the object to be measured irradiatedwith the intensity modulated light; and a container in which a spacebetween the light outgoing means and the acoustic wave detection meansis filled with an acoustic matching substance having acoustic impedancesubstantially equal to that of the object to be measured.

By instituting the container filled with the acoustic matching substancehaving the acoustic impedance substantially equal to that of the objectto be measured, the object to be measured is arranged in the containerfilled with the acoustic matching substance having the acousticimpedance substantially equal to that of the object to be measured, andthe photoacoustic signal from the object to be measured can be detectedunder the environment in which the object to be measured is surroundedby the acoustic matching substance. This configuration leads to analleviation of the attenuation which is caused by the reflection of thephotoacoustic signal at the boundary between the object to be measuredand the surroundings as well as at the contact between the object to bemeasured and the acoustic wave detection means.

In the constituent concentration measuring apparatus, it is desirablethat the light generating means generates two light beams havingdifferent wavelengths, and the light modulation means intensity-modulateeach of the light beams into the intensity modulated light beams, theintensity modulated light beams having the same frequency and reversephases.

The influence of the water on the photoacoustic signal can be removed byusing the two intensity modulated light beams having the differentwavelengths for the intensity modulated light. As for the modulation,the frequencies are equal and the phases are reversed to one another.

A constituent concentration measuring apparatus according to one aspectof the invention is characterized by comprising light generating meansfor generating light; light modulation means for electricallyintensity-modulating the light at a constant frequency, the light beinggenerated by the light generating means; light outgoing means foroutputting the intensity modulated light toward an object to bemeasured, the intensity modulated light being intensity-modulated by thelight modulation means; an acoustic wave generator which outputs anacoustic wave; and acoustic wave detection means for detecting theacoustic wave emitted from the object to be measured, which isirradiated with the intensity modulated light, and the acoustic wavetransmitted from the acoustic wave generator through the object to bemeasured.

One aspect of the invention is characterized in that, when theconstituent concentration which is the measurement objective of theobject to be measured is measured by the photoacoustic method, theultrasonic wave (in this case, referred to as acoustic wave) emittedfrom the acoustic wave generator which is placed near irradiationposition of the excitation light, i.e., near the source of photoacousticsignal is detected as a reference signal to search for the arrangementwhich optimizes a positional relationship between the photoacousticsignal source and the acoustic wave detection means. The photoacousticsignal is detected under the optimum arrangement, which allows theconstituent concentration to be measured using a propagation path whichminimizes the adverse influence of scatterers existing in the object tobe measured.

When the photoacoustic signal is detected in the arrangement in whichthe detected acoustic wave signal intensity becomes a predeterminedvalue such that the attenuation amount of acoustic wave is keptconstant, the photoacoustic signal can be detected while influences ofuncertain factors are eliminated. The uncertain factors include thechange in influence of the scatterers on the photoacoustic signal by thechange in positional relationship between the photoacoustic signalgeneration source and the acoustic wave detection means as well as bythe change at the contact between the acoustic wave detection means andthe object to be measured. Therefore, the constituent concentration canbe measured with no influence of the many parameters associated with thepositional change of the constituent concentration measuring apparatus.

According to one aspect of the invention, the influence of thereflecting/scattering scatterers on the photoacoustic signal can beprobed using the acoustic wave. Therefore, the photoacoustic signal canbe detected with the optimum arrangement.

In searching the optimal arrangement of the devices in terms of theobject to be measured in a measuring system by the photoacoustic method,means for adjusting the arrangement is mechanized to operateconcurrently with the acoustic wave detection means, which allows theconstituent concentration measurement to be automated to operate alwaysunder the optimum arrangement. In the invention, the intensity modulatedlight which is modulated by the constant frequency is used as theexcitation light.

According to one aspect of the invention, the influence of thereflecting/scattering scatterers on the photoacoustic signal can beprobed using the acoustic wave. Therefore, the photoacoustic signal canbe detected with the optimum arrangement.

A constituent concentration measuring apparatus according to one aspectof the invention is characterized by comprising light generating meansfor generating two light beams having different wavelengths; lightmodulation means for electrically intensity-modulating each of the twolight beams having the mutually different wavelengths using signalshaving the same frequency and reverse phases; light outgoing means foroutputting the two intensity-modulated light beams having the mutuallydifferent wavelengths toward an object to be measured; and acoustic wavedetection means for detecting an acoustic wave emitted from the objectto be measured by the outputted light.

In one aspect of the invention, each of the two light beams having themutually different wavelengths is electrically intensity-modulated usingthe signals having the same frequency and reverse phases, so that theacoustic wave corresponding to each of the two light beams having themutually different wavelengths can be detected with no influence from afrequency dependence of the acoustic wave detection means.

One of the two light beams generates acoustic wave having the pressurecorresponding to the total absorption in the state where the constituentof the measuring object and water are mixed together in the object to bemeasured, and the other light beam generates the acoustic wave havingthe pressure originating only from the water occupying the large part ofthe object to be measured, so that the pressure of the acoustic wavegenerated only by the constituent of the measuring object is detectableas the difference between two acoustic waves. As a result, quantity ofthe constitute in the measuring object can be measured.

With the two acoustic wave pressures, one generated by one of the twolight beams corresponding to the total absorption in the state where theconstituent of the measuring object and water are mixed together in theobject to be measured, while another generated by the other light beamcorresponding only to the water occupying the large part of the objectto be measured, their frequencies are equal to each other and the phaseare reversed to each other, therefore, the pressures are superposed toeach other in the form of acoustic wave in the object to be measured,and the difference in pressure of the acoustic waves is directlydetected. Accordingly, the difference in pressure of the acoustic wavescan be obtained more accurately rather than by computing the differencefrom separate measurements of the pressure of the acoustic wavegenerated by one of the two light beams corresponding to the totalabsorption in the state where the constituent of the measuring objectand water are mixed together in the object to be measured, as well as ofthe pressure of the acoustic wave generated by the other light beamcorresponding only to the water occupying the large part of the objectto be measured. The above point constitutes a novel advantage which doesnot exist in the conventional techniques.

In one aspect of the invention, the modulation frequency by which thetwo light beams having the mutually different wavelengths areelectrically intensity-modulated can be set to the resonant frequencyconcerning the detection of the acoustic wave generated in the object tobe measured. The photoacoustic signal is measured for the two lightbeams having mutually different wavelengths are selected by aconsideration on the non-linearity regarding to the absorptioncoefficient in the measured value of the photoacoustic signal. Then, theacoustic wave generated in the object to be measured can be measuredwith a high accuracy from the measured values while the influences ofthe many parameters which are hardly kept constant, are eliminated.

In the constituent concentration measuring apparatus, the constituentconcentration measuring apparatus further comprises frequency sweepmeans for sweeping a modulation frequency, the light generated by thelight generating means being modulated in the modulation frequency; andintegration means for integrating the acoustic wave in a sweptmodulation frequency range, the acoustic wave being detected by theacoustic wave detection means, the constituent concentration measuringapparatus characterized in that the light modulation means electricallyintensity-modulate each of the two light beams having the mutuallydifferent wavelengths using the frequency sweep means and with mutuallyreverse modulation phases.

In one aspect of the invention, the photoacoustic signal generated inthe object to be measured is integrated in the swept modulation signalrange. The photoacoustic signal exploiting the high sensitivity in thefrequency corresponding to the resonance frequency of the acoustic wavedetection means is integrated even if the resonance frequency of theacoustic wave detection means suffers a drift. Thus the measurement canbe performed always with the high-sensitivity resonance frequency.

In the constituent concentration measuring apparatus, it is desirablethat the acoustic wave detection means track the modulation frequency todetect the acoustic wave emitted in the object to be measured, themodulation frequency being swept by the frequency sweep means, and theintegration means integrate the acoustic wave in the modulationfrequency range where the acoustic wave detection means has highdetection sensitivity, the acoustic wave being detected by the acousticwave detection means.

In one aspect of the invention, in the case where the resonancefrequency of the acoustic wave detection means happens to change, thechange in resonance frequency of the acoustic wave detection means inwhich the detection sensitivity becomes the maximum is determined fromthe result on the measurement of the photoacoustic signal emitted in theobject to be measured by the irradiation light which is modulated by thefrequency-swept modulation frequency, and the change in resonancefrequency is tracked to integrate the detected value of thephotoacoustic signal near the resonance frequency.

In the constituent concentration measuring apparatus, it is desirable tofurther comprise liquid constituent concentration computation means forcomputing a constituent concentration of a liquid constituent from theacoustic wave integrated by the integration means, the liquidconstituent being set as a measuring object in the object to bemeasured.

In one aspect of the invention, theoretical or experimental valuesshowing the relationship between the photoacoustic signal generated inthe object to be measured and the constituent concentration set as themeasuring object are prepared beforehand, and the constituentconcentration of the measuring object is computed based on the detectedvalue of the photoacoustic signal generated in the object to bemeasured.

In the constituent concentration measuring apparatus, the constituentconcentration measuring apparatus further comprises an acoustic wavegenerator which outputs an acoustic wave, and it is desirable that theacoustic wave detection means detects the acoustic wave emitted from theobject to be measured as well as said acoustic wave transmitted from theacoustic wave generator through the object to be measured.

According to one aspect of the invention, the influence of thereflecting/scattering scatterers on the photoacoustic signal can beprobed using the acoustic wave. Therefore, the photoacoustic signal canbe detected with the optimum arrangement.

In the constituent concentration measuring apparatus, it is desirable tofurther comprise drive means for varying at least one of positions ofthe acoustic wave generator and the acoustic wave detection means.

According to one aspect of the invention, the influence of thereflecting/scattering scatterers on the photoacoustic signal can beprobed for each propagation path by changing the acoustic wavepropagation path. Thus, the photoacoustic signal can be detected in theprobed optimum arrangement.

In the constituent concentration measuring apparatus, it is desirable tofurther comprise control means for controlling the drive means such thatintensity of the acoustic wave detected by the acoustic wave detectionmeans becomes a particular value.

According to one aspect of the invention, the photoacoustic signal isautomatically made to be detected in the probed optimum arrangement.

In the constituent concentration measuring apparatus, it is desirablethat the light generating means set the light wavelengths of the twolight beams to two light wavelengths where an absorption differenceexhibited by the liquid constituent set as the measuring object islarger than the absorption difference exhibited by a solvent.

In the constituent concentration measuring apparatus, it is desirablethat the light generating means sets one of the light wavelengths of thetwo light beams to a light wavelength where the liquid constituent setas the measuring object exhibits characteristic absorption, and thelight generating means sets the other light wavelength to a wavelengthwhere the solvent exhibits an equal absorption to that for the one ofthe light wavelengths.

One aspect of the invention is the case where the difference inabsorption exhibited by the solvent is set to zero, in the lightgenerating means in the constituent concentration measuring apparatus inwhich the light wavelengths of the two light beams are set to two lightwavelengths so that the absorption difference exhibited by the liquidconstituent set as the measuring object is larger than the absorptiondifference exhibited by the solvent. Therefore, the influence by theabsorption of the solvent can be eliminated.

In the constituent concentration measuring apparatus, it is desirablethat the light wavelengths of the two light beams are set to twowavelengths where an absorption difference exhibited by the liquidconstituent set as the measuring object is larger than the absorptiondifference exhibited by other liquid constituents.

In the constituent concentration measuring apparatus, it is desirable tofurther comprise a coupler between the light outgoing means and theobject to be measured, the coupler combining the outgoing light beams.

The light can be focused on the measurement region, so that thephotoacoustic signal can efficiently be generated.

In the constituent concentration measuring apparatus, it is desirable tofurther comprise rectifying amplification means for detecting amplitudeof the acoustic wave from the acoustic wave detection means.

The amplitude of the acoustic wave can be detected from the detectedphotoacoustic signal.

In the constituent concentration measuring apparatus, it is desirable tofurther comprise liquid constituent concentration computation means forcomputing a constituent concentration of a liquid constituent frompressure of the detected acoustic wave, the liquid constituent being setas a measuring object in the object to be measured.

In the constituent concentration measuring apparatus, it is desirable tofurther comprise recording means for recording the acoustic wave as afunction of the modulation frequency, the acoustic wave being detectedby the acoustic wave detection means.

By including the means for recording the photoacoustic signal detectedby the acoustic wave detection means for each swept modulationfrequency, if the resonance frequency of the acoustic wave detectionmeans happens to change, still the modulation frequency sweep range ofthe irradiating light covers the range in which the resonance frequencypossibly changes, the values measured with high accuracy can be selectedfrom the detected photoacoustic signals, which are integrated andaveraged to confirm that the constituent concentration is correctlymeasured.

A constituent concentration measuring apparatus according to one aspectof the invention is characterized by comprising light generating meansfor generating light; frequency sweep means for sweeping a modulationfrequency, the light generated by the light generating means beingmodulated in the modulation frequency; light modulation means forelectrically intensity-modulating the light using a signal from thefrequency sweep means, the light being generated by the light generatingmeans; light outgoing means for outputting the intensity-modulated lighttoward a test subject; acoustic wave detection means for detecting anacoustic wave which is emitted in the test subject by the outputtedlight; and integration means for integrating the acoustic wave in aswept modulation frequency range, the acoustic wave being detected bythe acoustic wave detection means.

In one aspect of the invention, the light is electricallyintensity-modulated using the modulation signal whose frequency is sweptin a predetermined range, the test subject is irradiated with theintensity-modulated light to detect the photoacoustic signal which is anacoustic wave generated in the test subject by the irradiation light,and the detected photoacoustic signal is integrated to compute theconstituent concentration which is the measurement objective in the testsubject. At this point, the wavelength of the light with which the testsubject is irradiated is set at the wavelength in which the constituentset as the measuring object exhibits the absorption. Thus, the change insensitivity characteristics of the acoustic wave detection means can betracked to measure the constituent concentration which is themeasurement objective at the frequency where the optimal sensitivity isattainable.

A constituent concentration measuring apparatus according to one aspectof the invention comprising light generating means for generating light;light modulation means for electrically intensity-modulating the lightat a constant frequency, the light being generated by the lightgenerating means; light outgoing means for outputting the intensitymodulated light toward a test subject, the intensity modulated lightbeing intensity-modulated by the light modulation means; and acousticwave detection means for detecting an acoustic wave which is emittedfrom the test subject irradiated with the intensity modulated light, theconstituent concentration measuring apparatus is characterized in thatan acoustic matching substance and the test subject can be arrangedbetween the light outgoing means and the acoustic wave detection means,the acoustic matching substance having acoustic impedance substantiallyequal to that of the test subject.

One aspect of the invention is characterized in that the photoacousticsignal is detected under the environment whose acoustic impedance issubstantially equal to that of the test subject. The test subject isirradiated with a light intensity modulated at a constant frequency, thephotoacoustic signal which is the acoustic wave emitted from the testsubject to be measured is detected to measure the concentration of aparticular constituent contained in the liquid by the acoustic wavedetection means though the acoustic matching substance. The acousticwave detection means detects the photoacoustic signal through theacoustic matching substance, which alleviates the signal loss caused byreflection of the acoustic wave. The reflection of the photoacousticsignal is caused by a boundary reflection between the test subject andsurroundings, and the reflection of the photoacoustic signal is alsooccurs at the contact between the test subject and the acoustic wavedetection means. Here the test subject and the acoustic matchingsubstance having the acoustic impedance substantially equal to that ofthe test subject can be arranged between the light outgoing means andthe acoustic wave detection means. Thus reflection at the boundarybetween the test subject and surroundings can be decreased.

A constituent concentration measuring apparatus according to one aspectof the invention is characterized by comprising light generating meansfor generating light; light modulation means for electricallyintensity-modulating the light at a constant frequency, the light beinggenerated by the light generating means; light outgoing means foroutputting the intensity modulated light toward a test subject, theintensity modulated light being intensity-modulated by the lightmodulation means; acoustic wave detection means for detecting anacoustic wave which is emitted from the test subject irradiated with theintensity modulated light; and a container in which a space between thelight outgoing means and the acoustic wave detection means is filledwith an acoustic matching substance having acoustic impedancesubstantially equal to that of the test subject.

By instituting the container filled with the acoustic matching substancehaving the acoustic impedance substantially equal to that of the testobject to be measured, the test subject to be measured is arranged inthe container filled with the acoustic matching substance having theacoustic impedance substantially equal to that of the test subject to bemeasured, and the photoacoustic signal from the test subject to bemeasured can be detected under the environment in which the test subjectto be measured is surrounded by the acoustic matching substance. Thisconfiguration leads to an alleviation of the attenuation which is causedby the reflection of the photoacoustic signal at the boundary betweenthe test subject to be measured and the surroundings as well as at thecontact between the test subject to be measured and the acoustic wavedetection means.

In the constituent concentration measuring apparatus, it is desirablethat the container is filled with water as for the acoustic matchingsubstance.

Because the acoustic impedance of the test subject is very close to thatof the water, a detection of the photoacoustic signal under theenvironment where the test subject is surrounded by the water candecrease the attenuation of the photoacoustic signal due to thereflection which is caused by the boundary reflection between the testsubject and the surroundings and by the contact between the test subjectand the acoustic wave detection means.

In the constituent concentration measuring apparatus, it is desirablethat the light generating means generates two light beams havingdifferent wavelengths, and the light modulation means intensity-modulateeach of the light beams into the intensity modulated light beams, theintensity modulated light beams having the same frequency and reversephases.

The influence of the water on the photoacoustic signal can be removed byusing the two intensity modulated light beams having the differentwavelengths for the intensity modulated light. As for the modulation,the frequencies are equal and the phases are reversed to one another.

In the constituent concentration measuring apparatus, it is desirablethat a cross-sectional shape of the container is a semicircle, and thelight outgoing means is positioned substantially at the center of thesemicircle.

The cross-sectional shape of the inner wall surface of the containerforms a semicircle, and the light outgoing means is arranged at thecenter of the circle. Therefore, the distance between the light outgoingmeans and the container side corresponding to an arc portion of thesemicircle can be kept constant. Moreover, the distance between thelight outgoing means and the container side corresponding to an arcportion of the semicircle is set to an extent in which the photoacousticsignal can be regarded as a plane wave, and the acoustic wave detectionmeans is arranged on the side, which allows the radially spreadingphotoacoustic signal to be efficiently detected. Thus, the accuracy ofphotoacoustic signal can further be increased by improving theefficiency of sound collection by the acoustic wave detection means.

In the constituent concentration measuring apparatus, it is desirablethat the two or more acoustic wave detection means are arranged on anarc portion of the semicircle of the container.

Two or more pieces of acoustic wave detection means are arranged in thecontainer side corresponding to the arc portion of the semicircle, whichallows the radially spreading photoacoustic signal to be detected moreefficiently with the acoustic wave detection means.

In the constituent concentration measuring apparatus, it is desirablethat a cross-sectional shape of the container is an ellipse, and thelight outgoing means and the acoustic wave detection means arepositioned substantially at the focal points of said ellipserespectively.

The cross-sectional shape of the inner wall surface formed an ellipse,and the light outgoing means and the acoustic wave detection means arearranged substantially at each of the two focal points of the ellipserespectively. Therefore, the photoacoustic signal can be scattered inthe container side and efficiently collected by the acoustic wavedetection means. Thus, the accuracy of photoacoustic signal can furtherbe increased by improving the efficiency of sound collection by theacoustic wave detection means.

In the constituent concentration measuring apparatus, it is desirablethat the bottom portion of the container forms a semi-ellipsoidcontaining the two focal points in sectional plane, and the lightoutgoing means and the acoustic wave detection means are positionedsubstantially at each of the two focal points of the semi-ellipsoidrespectively.

The bottom portion of the inner wall surface of the container forms asemi-ellipsoid containing the two focal points in sectional plane, andthe light outgoing means and the acoustic wave detection means arearranged at each of the two focal points of the semi-ellipsoidrespectively. Therefore, the photoacoustic signal can be scattered inthe bottom portion of the container and efficiently collected by theacoustic wave detection means. Thus, the accuracy of photoacousticsignal can further be increased by improving the efficiency of soundcollection by the acoustic wave detection means.

In the constituent concentration measuring apparatus, it is desirable tocomprise a reflection material on at least a part of the inner wall ofthe container.

The efficiency of collecting the photoacoustic signal onto the acousticwave detection means can be improved by overlaying the reflectionmaterial onto at least a part of the inner wall of the container. Thus,the accuracy of photoacoustic signal detected by the acoustic wavedetection means can further be increased.

In the constituent concentration measuring apparatus, it is desirable tocomprise a sound absorbing material on at least a part of the inner wallof the container.

The multiple-reflected acoustic wave caused by the inhomogeneity ofinternal structure of the test subject is absorbed and removed byoverlaying the sound absorbing material onto at least a part of theinner wall of the container, so that the photoacoustic signal emittedfrom the test subject can be detected efficiently. Therefore, theaccuracy of photoacoustic signal detected by the acoustic wave detectionmeans can further be increased.

In the constituent concentration measuring apparatus, it is desirable tofurther comprise an outgoing window on the inner wall of the container,the outgoing window being transparent for the intensity modulated light.

The container is furnished with an outgoing window transparent for theintensity modulated light, which allows the light outgoing means to beplaced outside the container. Therefore, the light outgoing means caneasily be arranged. The intensity modulated light can be outputted fromthe inner wall surface of the container, which allows the influence ofsurface irregularity on the inner wall of the container to be suppressedto decrease the reflection of the photoacoustic signal.

In the constituent concentration measuring apparatus, it is desirablethat the light outgoing means includes an optical fiber which guides theintensity modulated light to the container.

The light outgoing means includes the optical fiber. Therefore, thelight generating means and the light modulation means can be arranged ata place distant from the light outgoing means to guide the intensitymodulated light to the position where the test subject is irradiated.

In the constituent concentration measuring apparatus, it is desirable tofurther comprise temperature measuring means for measuring a temperatureof the acoustic matching substance; and temperature adjustment means foradjusting a temperature of the acoustic matching substance according tothe temperature being measured by the temperature measuring means.

The temperature adjustment means is included to adjust the temperatureof the acoustic matching substance according to the temperature measuredby the temperature measuring means, which allows to stabilizetemperature of the acoustic matching substance and the surface of thetest subject. Thus, the disturbance of the photoacoustic signalintensity by the temperature change can be decreased, which leads to animprovement of the S/N ratio of photoacoustic signal.

A constituent concentration measuring apparatus according to one aspectof the invention is characterized by comprising light generating meansfor generating light; light modulation means for electricallyintensity-modulating the light at a constant frequency, the light beinggenerated by the light generating means; light outgoing means foroutputting the intensity modulated light toward a test subject, theintensity modulated light being intensity-modulated by the lightmodulation means; an acoustic wave generator which outputs an acousticwave; and acoustic wave detection means for detecting the acoustic waveemitted from the test subject which is irradiated with the intensitymodulated light, as well as said acoustic wave transmitted from theacoustic wave generator through the test subject.

One aspect of the invention is characterized in that, when theconstituent concentration which is the measurement objective is measuredby the photoacoustic method, the ultrasonic wave (in this case, referredto as acoustic wave) emitted from the acoustic wave generator which isplaced near irradiation position of the excitation light, i.e., near thesource of photoacoustic signal is detected as a reference signal tosearch for the arrangement which optimizes a positional relationshipbetween the photoacoustic signal source and the acoustic wave detectionmeans. The photoacoustic signal is detected under the optimumarrangement, which allows the constituent concentration to be measuredusing a propagation path which minimizes the adverse influence ofscatterers existing in the test subject to be measured.

When the photoacoustic signal is detected in the arrangement in whichthe detected acoustic wave signal intensity becomes a predeterminedvalue such that the attenuation amount of acoustic wave is keptconstant, the photoacoustic signal can be detected while the influencesof uncertain factors are eliminated. The uncertain factors include thechange in influence of the scatterers on the photoacoustic signal by thechange in positional relationship between the photoacoustic signalgeneration source and the acoustic wave detection means as well as bythe change at the contact between the acoustic wave detection means andthe test subject. Therefore, the constituent concentration can bemeasured with no influence of the many parameters associated with thepositional change of the constituent concentration measuring apparatus.

In searching the optimal arrangement of the test subject particularlythe living body and the devices in terms of the object to be measured ina measuring system by the photoacoustic method, means for adjusting thearrangement is mechanized to operate concurrently with the acoustic wavedetection means, which allows the constituent concentration measurementto be automated to operate always under the optimum arrangement. In theinvention, the intensity modulated light which is modulated by theconstant frequency is used as the excitation light.

According to one aspect of the invention, the influence of thereflecting/scattering scatterers on the photoacoustic signal can beprobed using the acoustic wave. Therefore, the photoacoustic signal canbe detected with the optimum arrangement.

A constituent concentration measuring apparatus according to one aspectof the invention is characterized by comprising light generating meansfor generating two light beams having different wavelengths; lightmodulation means for electrically intensity-modulating each of the twolight beams having the mutually different wavelengths using signalshaving the same frequency and reverse phases; light outgoing means foroutputting the two intensity-modulated light beams having the mutuallydifferent wavelengths toward a test subject; and acoustic wave detectionmeans for detecting an acoustic wave emitted in the test subject by theoutputted light.

In one aspect of the invention, each of the two light beams having themutually different wavelengths is electrically intensity-modulated usingthe signals having the same frequency and reverse phases, so that theacoustic wave corresponding to each of the two light beams having themutually different wavelengths can be detected with no influence from afrequency dependence of the acoustic wave detection means.

One of the two light beams generates acoustic wave having the pressurecorresponding to the total absorption in the state where the constituentof the measuring object and water are mixed together in the testsubject, and the other light beam generates the acoustic wave having thepressure originating only from the water occupying the large part of thetest subject so that the pressure of the acoustic wave generated only bythe constituent of the measuring object is detectable as the differencebetween two acoustic waves. As a result, quantity of the constitute inthe measuring object can be measured.

With the two acoustic wave pressures, one generated by one of the twolight beams corresponding to the total absorption in the state where theconstituent of the measuring object and water are mixed together in thetest subject to be measured, while another generated by the other lightbeam corresponding only to the water occupying the large part of thetest subject to be measured, their frequencies are equal to each otherand the phase are reversed to each other, therefore, the pressures aresuperposed to each other in the form of acoustic wave in the testsubject, and the difference in pressure of the acoustic waves isdirectly detected. Accordingly, the difference in pressure of theacoustic waves can be obtained more accurately rather than by computingthe difference from separate measurement of the pressure of the acousticwave generated by one of the two light beams corresponding to the totalabsorption in the state where the constituent of the measuring objectand water are mixed together in the test subject to be measured, as wellas of the pressure of the acoustic wave generated by the other lightbeam corresponding only to the water occupying the large part of thetest subject. The above point constitutes a novel advantage which doesnot exist in the conventional techniques.

In one aspect of the invention, the modulation frequency by which thetwo light beams having the mutually different wavelengths areelectrically intensity-modulated can be set to the resonant frequencyconcerning the detection of the acoustic wave generated in the testsubject to be measured. The photoacoustic signal is measured for the twolight beams having mutually different wavelengths are selected by aconsideration on the non-linearity regarding to the absorptioncoefficient in the measured value of the photoacoustic signal. Then, theacoustic wave generated in the test subject can be measured with a highaccuracy from the measured values while the influences of the manyparameters which are hardly kept constant, are eliminated.

In the constituent concentration measuring apparatus, it is desirable tofurther comprise second light outgoing means for outputting the lighttoward the test subject, the light being intermittently emitted atintervals which are longer than the repetition period for the samefrequency.

According to one aspect of the invention, the photoacoustic signalemission amount by the absorption at the constituent, set as themeasuring object is increased in the test subject, particularly in theliving body tissue, so that the accurate constituent concentration canbe measured in the noninvasive manner.

In the constituent concentration measuring apparatus, it is desirablethat light from the second light outgoing means has a wavelength whichexhibits a characteristic absorption of a constituent different from theconstituent set as the measuring object.

Only the photoacoustic signal from the blood constituent can beincreased by raising the temperature of the blood tissue as comparedwith the non-blood tissue.

In the constituent concentration measuring apparatus, it is desirablethat light from the second light outgoing means has a wavelength whichexhibits a characteristic absorption of hemoglobin in blood.

Only the photoacoustic signal from the blood containing the hemoglobincan be increased by raising the temperature of the hemoglobin.

In the constituent concentration measuring apparatus, it is desirablethat an interval during which the second light outgoing means emits thelight is an interval during which temperature rise of 2° C. or less isresulted is generated in the test subject.

The influence on the test subject can be suppressed to the minimum.

In the constituent concentration measuring apparatus, it is desirablethat light intensity of the second light outgoing means is an intensityby which temperature rise of 2° C. or less is resulted in said testsubject.

The influence on the test subject can be suppressed to the minimum.

In the constituent concentration measuring apparatus, the constituentconcentration measuring apparatus further comprises frequency sweepmeans for sweeping a modulation frequency, the light generated by thelight generating means being modulated in the modulation frequency; andintegration means for integrating the acoustic wave in a sweptmodulation frequency range, the acoustic wave being detected by theacoustic wave detection means, and it is desirable that the lightmodulation means electrically intensity-modulate each of the two lightbeams having the mutually different wavelengths using the signal fromthe frequency sweep means and with mutually reverse modulation phases.

In one aspect of the invention, the photoacoustic signal generated inthe test subject is integrated in the swept modulation signal range. Thephotoacoustic signal exploiting the high sensitivity in the frequencycorresponding to the resonance frequency of the acoustic wave detectionmeans is integrated even if the resonance frequency of the acoustic wavedetection means suffers a drift. Thus measurement can be performedalways with the high-sensitivity resonance frequency.

In the constituent concentration measuring apparatus, it is desirablethat the acoustic wave detection means track the modulation frequency todetect the acoustic wave emitted in the test subject by the outputtedlight, the modulation frequency being swept by the frequency sweepmeans, and the integration means integrates the acoustic wave in themodulation frequency range where the acoustic wave detection means hashigh detection sensitivity, the acoustic wave being detected by theacoustic wave detection means.

In one aspect of the invention, in the case where the resonancefrequency of the acoustic wave detection means happens to change, thechange in resonance frequency of the acoustic wave detection means inwhich the detection sensitivity becomes the maximum is determined fromthe result on the measurement of the photoacoustic signal emitted in thetest subject to be measured by the irradiation light which is modulatedby the frequency-swept modulation frequency, and the change in resonancefrequency is tracked to integrate the detected value of thephotoacoustic signal near the resonance frequency.

In the constituent concentration measuring apparatus, it is desirable tofurther comprise constituent concentration computation means forcomputing a constituent concentration of a constituent from the acousticwave integrated by said integration means, the constituent being set asa measuring object in the said test subject.

In one aspect of the invention, theoretical or experimental valuesshowing the relationship between the photoacoustic signal generated inthe test subject and the constituent concentration set as the measuringobject are prepared beforehand, and the constituent concentration of themeasuring object is computed based on the detected value of thephotoacoustic signal generated in the test subject.

In the constituent concentration measuring apparatus, the constituentconcentration measuring apparatus further comprises an acoustic wavegenerator which outputs an acoustic wave, and it is desirable that theacoustic wave detection means detect the acoustic wave emitted from thetest subject as well as said acoustic wave transmitted from the acousticwave generator through the test subject.

According to one aspect of the invention, the influence of thereflecting/scattering scatterers on the photoacoustic signal can beprobed using the acoustic wave. Therefore, the photoacoustic signal canbe detected with the optimum arrangement.

In the constituent concentration measuring apparatus, it is desirable tofurther comprise drive means for varying at least one of positions ofthe acoustic wave generator and the acoustic wave detection means.

According to one aspect of the invention, the influence of thereflecting/scattering scatterers on the photoacoustic signal can beprobed for each propagation path by changing the acoustic wavepropagation path. Thus, the photoacoustic signal can be detected in theprobed optimum arrangement.

In the constituent concentration measuring apparatus, it is desirable tofurther comprise control means for controlling the drive means such thatintensity of the acoustic wave detected by the acoustic wave detectionmeans becomes a particular value.

According to one aspect of the invention, the photoacoustic signal isautomatically made to be detected in the probed optimum arrangement.

In the constituent concentration measuring apparatus, it is desirablethat the light outgoing means is fixed to the acoustic wave generator soas to keep the relative position to the acoustic wave generator.

According to one aspect of the invention, since the relative positionbetween the light outgoing means and the acoustic wave generator isfixed, the former can automatically be moved to the optimum positionfollowing the latter acoustic wave generator.

In the constituent concentration measuring apparatus, it is desirable tofurther comprise pressing means for pressing the acoustic wave generatorand the acoustic wave detection means against the test subject withpressing force whose pressure can be controlled.

According to one aspect of the invention, since the pressure forpressing the acoustic wave generator and the acoustic wave detectionmeans against the test subject is controllable, the pressure at whichthe acoustic wave generator and the acoustic wave detection means comeinto contact with the test subject can be kept at a predetermined value.Therefore, the influence of the pressure on the test subject can bereduced.

In the constituent concentration measuring apparatus, it is desirablethat the acoustic wave generator is placed in proximity of the intensitymodulated light beam outputted from the light outgoing means.

According to one aspect of the invention, since the acoustic wave isoutputted to a position close to the path of the intensity modulatedlight beam, the reflection/scattering can be examined more precisely forthe propagation path of the photoacoustic signal.

In the constituent concentration measuring apparatus, it is desirable tofurther comprise a transmission window in a part of the acoustic wavegenerator, the transmission window transmitting said intensity modulatedlight beam.

According to one aspect of the invention, the test subject can beirradiated with the intensity modulated light through the acoustic wavegenerator. Therefore, the test subject can be irradiated with theintensity modulated light from the optimum position of the acoustic wavegenerator.

In the constituent concentration measuring apparatus, it is desirablethat the frequency and/or the intensity of said outputted acoustic wavefrom said acoustic wave generator is variable.

According to one aspect of the invention, scatterers can be probed withthe acoustic wave having the frequency equal to that of thephotoacoustic signal detected by the acoustic wave detection means, sothat the influence of the scatterers on the photoacoustic signal can beexamined more correctly. The intensity of the acoustic wave outputtedfrom the acoustic wave generator can be increased or decreased accordingto the intensity of the acoustic wave detected by the acoustic wavedetection means, so that the detected intensity can be compared even ifthe intensity detected by the acoustic wave detection means is small.

In the constituent concentration measuring apparatus, it is desirable tofurther comprise an acoustic coupling element on the surface of theacoustic wave generator and/or the light outgoing means, the surfacebeing in contact with the test subject, the acoustic coupling elementhaving an acoustic impedance substantially equal to that of the testsubject.

According to one aspect of the invention, the reflection/scattering canbe reduced at the surface in which at least one of the acoustic wavegenerator and the acoustic wave detection means comes into contact withthe test subject.

In the constituent concentration measuring apparatus, it is desirablethat the light generating means sets the light wavelengths of the twolight beams to two wavelengths where an absorption difference exhibitedby the constituent set as the measuring object is larger than theabsorption difference exhibited by a solvent.

In the constituent concentration measuring apparatus, it is desirablethat the light generating means sets one of the light wavelengths of thetwo light beams to a light wavelength where the constituent set as themeasuring object exhibits characteristic absorption, and the lightgenerating means set the other light wavelength to a wavelength wherethe solvent exhibits an equal absorption to that for the one of thelight wavelengths.

One aspect of the invention is the case where the difference inabsorption exhibited by the solvent is set to zero, in the lightgenerating means in the constituent concentration measuring apparatus inwhich the light wavelengths of the two light beams are set to two lightwavelengths so that the absorption difference exhibited by theconstituent set as the measuring object is larger than the absorptiondifference exhibited by the solvent. Therefore, the influence by theabsorption of the solvent can be eliminated.

In the constituent concentration measuring apparatus, it is desirablethat the light wavelengths of said two light beams are set to twowavelengths where an absorption difference exhibited by the constituentset as the measuring object is larger than the absorption differenceexhibited by other constituents.

In the constituent concentration measuring apparatus, it is desirablethat the light generating means sets the light wavelengths of the twolight beams to two wavelengths where an absorption difference exhibitedby the blood constituent set as the measuring object is larger than theabsorption difference exhibited by a water.

In the constituent concentration measuring apparatus, it is desirablethat the light generating means sets one of the light wavelengths of thetwo light beams to a light wavelength where the blood constituent set asthe measuring object exhibits characteristic absorption, and the lightgenerating means sets the other light wavelength to a wavelength where awater exhibits an equal absorption to that for the one of the lightwavelengths.

One aspect of the invention is the case where the difference inabsorption exhibited by the water is set to zero, in the lightgenerating means in the constituent concentration measuring apparatus inwhich the light wavelengths of the two light beams are set to two lightwavelengths so that the absorption difference exhibited by the bloodconstituent set as the measuring object is larger than the absorptiondifference exhibited by the water. Therefore, the influence by theabsorption of the water can be eliminated.

In the constituent concentration measuring apparatus, it is desirablethat the light wavelengths of the two light beams are set to twowavelengths where an absorption difference exhibited by the bloodconstituent set as the measuring object is larger than the absorptiondifference exhibited by other blood constituents.

In the constituent concentration measuring apparatus, it is desirable tofurther comprise a coupler between the light outgoing means and the testsubject, the coupler combining the outgoing light beams.

The light can be focused on the measurement region, so that thephotoacoustic signal can efficiently be generated.

In the constituent concentration measuring apparatus, it is desirable tofurther comprise rectifying amplification means for detecting amplitudeof the acoustic wave from the acoustic wave detection means.

The amplitude of the acoustic wave can be detected from the detectedphotoacoustic signal.

In the constituent concentration measuring apparatus, it is desirablethat the rectifying amplification means is a phase sensitive amplifier.

The amplitude of the acoustic wave can be detected from thephotoacoustic signal with a high sensitivity.

In the constituent concentration measuring apparatus, it is desirablethat diameters of the two outgoing light beams from the light outgoingmeans are substantially equal to each other.

The measurement accuracy can be improved by matching the measurementregions.

In the constituent concentration measuring apparatus, it is desirable tofurther comprise constituent concentration computation means forcomputing a constituent concentration of a constituent from pressure ofthe detected acoustic wave, the constituent being set as a measuringobject in the test subject.

In the constituent concentration measuring apparatus, it is desirablethat the constituent concentration computation means divide pressure ofthe acoustic wave, which is emitted by irradiating the two light beamshaving the mutually different wavelengths to the test subject, bypressure of the acoustic wave which is emitted when one of the two lightbeams is set to zero power.

As described above, the pressure of the acoustic wave generated byirradiating the test subject with the two light beams having themutually different wavelengths is detected as the difference between thepressure of the acoustic wave generated by one of the two light beamscorresponding to the total absorption in the state where the constituentof the measuring object and water are mixed together in the test subjectand the pressure of the acoustic wave generated by the other light beamcorresponding to the water alone occupying the large part of the testsubject. The constituent concentration can be measured by dividing thedifference by the acoustic wave pressure generated when one of the twolight beams is set to zero power, i.e., the acoustic wave pressuregenerated solely by the water occupying the large part of the testsubject according to the later-mentioned formula (5).

In the constituent concentration measuring apparatus, it is desirablethat the light modulation means operates at the same frequency as aresonant frequency concerning detection of the acoustic wave generatedin the test subject.

In one aspect of the invention, the modulation frequency by which thetwo light beams having the mutually different wavelengths areelectrically intensity-modulated is set to the same frequency as theresonant frequency concerning the detection of the acoustic wavegenerated in the test subject. Therefore, the acoustic wave generated inthe test subject can be measured with high accuracy.

In the constituent concentration measuring apparatus, it is desirablethat the light generating means adjusts relative intensity of the twolight beams having the mutually different wavelengths such that pressureof the acoustic wave becomes zero, the acoustic wave being generated bycombining said two intensity-modulated light beams having the differentwavelengths into a single light beam to irradiate water.

According to the above calibration, the relative intensity between thetwo light beams having the mutually different wavelengths can be setsuch that the intensity of the photoacoustic signal emitted from thewater occupying the large part of test subject is equalized for thewavelengths of two light beams. Consequently for the whole system formeasuring photoacoustic signal, the relative intensity between the twolight beams having the mutually different wavelengths can be calibratedto improve the measurement accuracy.

In the constituent concentration measuring apparatus, it is desirablethat the acoustic wave detection means is synchronized with themodulation frequency to detect the acoustic wave by phase sensitivedetection.

The photoacoustic signal is detected by the phase-sensitive detectionsynchronized with the modulation frequency, so that the detection can beperformed with a high accuracy.

In the constituent concentration measuring apparatus, it is desirablethat the light generating means and the light modulation consists of twodirectly-modulated semiconductor laser light sources driven byrectangular-waveform signals having the same frequency and reversephases.

In one aspect of the invention, the two light beams having the mutuallydifferent wavelengths can be generated and at the same time be modulatedby using two directly-modulated semiconductor laser light sources drivenby rectangular-waveform signals having the same frequency and reversephases, so that the apparatus configuration can be simplified.

In the constituent concentration measuring apparatus, it is desirablethat a blood constituent which is set as the measuring object is glucoseor cholesterol.

In the case where the concentration of glucose or cholesterol ismeasured, the measurement can accurately be performed by irradiating thetest subject with the light having the wavelength exhibiting thecharacteristic absorption.

In the constituent concentration measuring apparatus, it is desirable tofurther comprise recording means for recording the acoustic wave as afunction of the modulation frequency, the acoustic wave being detectedby the acoustic wave detection means.

By including the means for recording the photoacoustic signal detectedby the acoustic wave detection means for each swept modulationfrequency, if the resonance frequency of the acoustic wave detectionmeans happens to change, still the modulation frequency sweep range ofthe irradiating light covers the range in which the resonance frequencypossibly changes, the values measured with high accuracy can be selectedfrom the detected photoacoustic signals, which are integrated andaveraged to confirm that the constituent concentration is correctlymeasured.

In the constituent concentration measuring apparatus, it is desirablethat the light outgoing means and the acoustic wave detection means arearranged at positions substantially opposing to each other.

In the photoacoustic signal emitted from the test subject, the largestsignal intensity is detected in the direction in which the lightoutgoing means outputs the intensity modulated light. The accuracy ofthe photoacoustic signal detected with the acoustic wave detection meanscan further be improved by arranging the light outgoing means and theacoustic wave detection means at positions such that the light outgoingmeans and the acoustic wave detection means oppose to each other.

In the constituent concentration measuring apparatus, it is desirable tofurther comprise a light shielding hood surrounding at least a part ofthe optical path of the intensity modulated light, the light shieldinghood preventing the intensity modulated light from leaking to theoutside of the constituent concentration measuring apparatus.

According to one aspect of the invention, the intensity modulated lightcan be prevented from leaking to the outside of the constituentconcentration measuring apparatus such as to a portion of the testsubject other than potion for the testing.

In the constituent concentration measuring apparatus, it is desirable tofurther comprise enduing means in which at least the light outgoingmeans and the acoustic wave detection means are arranged in a portionwhich comes into contact with the test subject, the portion beinglocated inside of an annular portion which is endued surrounding thetest subject.

As described above, at least the light irradiation unit and the acousticwave detection means, are inlaid onto an accessory having the annularportion which is endued surrounding the test subject. Thus, the changein distance between the light outgoing means and the acoustic wavedetection means caused by the movement of the test subject, i.e., thechange in thickness of a part of the test subject which is the measuringobject located between the light outgoing means and the acoustic wavedetection means is suppressed to stabilize the measured value of theacoustic wave emitted from the test subject during the measurement. Inaddition, deformation of the peripheries of the measurement portion inthe test subject is prevented, which stabilizes the multiple reflectionsfrom peripheries of the measurement portion in the test subject. As aresult, the constituent concentration set as the measuring object cancorrectly be measured.

In the constituent concentration measuring apparatus, it is desirablethat the light outgoing means and the acoustic wave detection means arearranged at positions substantially opposing to each other in theannular portion of the enduing means.

As described above, the light outgoing means and the acoustic wavedetection means are arranged at the positions where the light outgoingmeans and the acoustic wave detection means oppose to each other onannular potion of the enduing means. Thus, when the light outgoing meansirradiates the test subject with the light, the acoustic wave detectionmeans efficiently detects the resulting acoustic wave emitted from thetest subject, and the constituent concentration set as the measuringobject can be accurately measured in the test subject.

In the constituent concentration measuring apparatus, it is desirablethat a layer of cushioning material covers at least a semicircularportion being in contact with the test subject inside the annularportion of said enduing means, the semicircular portion comprisingposition where said acoustic wave detection means is inlaid, thecushioning material having acoustic impedance approximately equal tothat of the test subject.

As described above, the layer of cushioning material covers at least thesemicircular portion being in contact with the test subject inside theannular portion of the enduing means, the semicircular portion includesthe position where the acoustic wave detection means is arranged, andthe cushioning material has the acoustic impedance approximately equalto that of test subject. Thus, of the acoustic wave emitted from thetest subject, a part which directly reaches the acoustic wave detectionmeans is efficiently detected, while the amount of acoustic wave emittedfrom the test subject which becomes a noise, is decreased which allowsthe constituent concentration to be measured more correctly. Theacoustic wave which becomes the noise, is received by the acoustic wavedetection means after multiple reflections generated at the interfacebetween the test subject and the enduing means inside the annularportion.

In the constituent concentration measuring apparatus, it is desirablethat a space between said layer of cushioning material and a innersurface of the annular portion of said enduing means is filled with asound absorbing material.

As described above, the space between the layer of cushioning materialand the inner surface on the annular portion of the enduing means isfilled with the sound absorbing material. Thus, the constituentconcentration can be measured more correctly by decreasing the amount ofacoustic wave which becomes the noise in the acoustic wave emitted fromthe test subject. The acoustic wave which becomes the noise, is detectedby the acoustic wave detection means after multiple reflectionsgenerated at the interface between the test subject and the enduingmeans inside the annular portion.

In the constituent concentration measuring apparatus, it is desirablethat said light generating means generates two light beams havingdifferent wavelengths by multiple semiconductor laser devices.

As described above, the light generating means generates the two lightbeams having different wavelengths by the multiple semiconductor laserdevices, which enables significant miniaturization and weight reductionof the constituent concentration measuring apparatus of the invention.

In the constituent concentration measuring apparatus, it is desirablethat the light outgoing means includes a beam expander which enlargesthe light beam diameter generated by said light generating means.

As described above, the light outgoing means includes the beam expanderwhich enlarges the light beam diameter generated by the light generatingmeans. Thus, the light beam with which the test subject is irradiated isenlarged, and the test subject can be irradiated with the relativelystrong light without adverse influence on the test subject, so that theconstituent concentration set as the measuring object can be measuredmore correctly in the test subject.

In the constituent concentration measuring apparatus, it is desirablethat the enduing means is a ring fitted in a human finger, said lightoutgoing means is arranged on a dorsal side of said finger, while saidacoustic wave detection means is arranged on a palm side of said finger.

As described above, the enduing means is the ring fitted to the humanfinger, the light outgoing means is arranged on the dorsal side of thefinger, while the acoustic wave detection means is arranged on the palmside of the finger. Thus, the acoustic wave detection means easily comesinto contact with the relatively soft skin of the finger, and theacoustic wave detection means can efficiently measure the acoustic wavegenerated in the finger, so that the constituent concentration can bemeasured more correctly. Further, the light outgoing means and theacoustic wave detection means are mounted in the inner surface of thering, which allows the constituent concentration of the human body to beeasily and continuously measured without imposing inconvenience for adaily life.

In the constituent concentration measuring apparatus, it is desirablethat the enduing means is a bracelet fitted in a human arm, said lightoutgoing means is arranged on a palm side of a hand, and said acousticwave detection means is arranged on a dorsal side of a hand.

As described above, the enduing means is the bracelet fitted on a humanarm, the light outgoing means is arranged on the palm side on the hand,and the acoustic wave detection means is arranged on the dorsal side onthe hand. Therefore, the acoustic wave detection means easily comes intocontact with the relatively soft skin of the arm, and the acoustic wavedetection means can efficiently measure the acoustic wave generated inthe arm, so that the constituent concentration can be measured morecorrectly. Further, the light outgoing means and the acoustic wavedetection means are mounted in the inner surface of the bracelet, whichallows the constituent concentration of the human body to be easily andcontinuously measured without imposing inconvenience for a daily life.

A constituent concentration measuring apparatus controlling methodaccording to one aspect of the invention is characterized bysequentially comprising a light generating procedure in which lightgenerating means generates light; a frequency sweep procedure in whichfrequency sweep means sweeps a modulation frequency, the light generatedin the light generating procedure being modulated in the modulationfrequency; a light modulation procedure in which light modulation meanselectrically intensity-modulates the light using a signal swept in thefrequency sweep procedure, the light being generated in the lightgenerating procedure; a light outgoing procedure in which light outgoingmeans outputs the light toward an object to be measured, the light beingintensity-modulated in the light modulation procedure; an acoustic wavedetection procedure in which acoustic wave detection means detects anacoustic wave which is generated in the object to be measured by thelight outputted in the light outgoing procedure; and an integrationprocedure in which integration means integrates the acoustic wave in aswept modulation frequency range, the acoustic wave being detected inthe acoustic wave detection procedure.

In one aspect of the invention, the light is electricallyintensity-modulated using the modulation signal whose frequency is sweptin a predetermined range, the intensity-modulated light is outputted,the photoacoustic signal generated by the outputted light is detected,and the detected photoacoustic signal is integrated to compute theconstituent concentration which is the measurement objective in theobject to be measured. At this point, the wavelength of the outputtedlight is set at the wavelength in which the constituent set as themeasuring object exhibits the absorption. Thus, the change insensitivity characteristics of the acoustic wave detection means can betracked to measure the constituent concentration which is themeasurement objective at the frequency where the optimal sensitivity isattainable.

A constituent concentration measuring apparatus controlling methodaccording to one aspect of the invention comprising a light generatingprocedure in which light generating means generates light; a lightmodulation procedure in which light modulation means electricallyintensity-modulates the light at a constant frequency, the light beinggenerated by said light generating procedure; a light outgoing procedurein which light outgoing means outputs the intensity modulated lighttoward an object to be measured, the intensity modulated light beingintensity-modulated by said light modulation procedure; and an acousticwave detection procedure in which acoustic wave detection means detectsan acoustic wave which is emitted from said object to be measured bysaid intensity modulated light in said light outgoing procedure, theconstituent concentration measuring apparatus controlling methodcharacterized in that said light outgoing procedure and said acousticwave detection procedure are performed in a container which is filledwith an acoustic matching substance having acoustic impedancesubstantially equal to that of the object to be measured.

One aspect of the invention is characterized in that the photoacousticsignal is detected under the environment whose acoustic impedance issubstantially equal to that of the object to be measured. A lightintensity-modulated at a constant frequency is outputted, and thephotoacoustic signal which is the acoustic wave generated by theoutputted light is detected to measure the concentration of a particularconstituent contained in the object to be measured by the acoustic wavedetection means though the acoustic matching substance. The lightoutgoing procedure and the acoustic wave detection procedure areperformed in the container which is filled with the acoustic matchingsubstance having acoustic impedance substantially equal to that of theobject to be measured. Thus, the photoacoustic signal can be detectedunder the environment in which the object to be measured is surroundedby the acoustic matching substance, and the attenuation can bedecreased. The attenuation is caused by the photoacoustic signalreflection at the boundary between the object to be measured andsurroundings, and also by dumping at the contact between the object tobe measured and the acoustic wave detection means.

A constituent concentration measuring apparatus controlling methodaccording to one aspect of the invention is characterized bysequentially comprising an optimum position detection procedure in whichacoustic wave generators output acoustic waves from two or moredifferent positions to object to be measured and acoustic wave detectionmeans detects a position where intensity of said acoustic wavetransmitted through said object to be measured becomes a particularvalue; and an acoustic wave detection procedure in which light outgoingmeans outputs intensity modulated light to said object to be measuredfrom the position where intensity of said acoustic wave becomes theparticular value, the intensity modulated light beingintensity-modulated at a constant frequency, and said acoustic wavedetection means detects the acoustic wave emitted from said object to bemeasured.

One aspect of the invention is characterized in that, when theconstituent concentration which is the measurement object is measured bythe photoacoustic method, the ultrasonic wave (in this case, referred toas acoustic wave) emitted from the acoustic wave generator which isplaced near irradiation position of the excitation light, i.e., nearsource of photoacoustic signal is detected as a reference signal tosearch for an arrangement which optimizes a positional relationshipbetween the photoacoustic signal source and the acoustic wave detectionmeans. The photoacoustic signal is detected under the optimumarrangement, which allows the constituent concentration to be measuredusing a propagation path which minimizes the adverse influence ofscatters on excitation light.

When the photoacoustic signal is detected in the arrangement in whichthe detected acoustic wave signal intensity becomes a predeterminedvalue such that the attenuation amount of acoustic wave is keptconstant, the photoacoustic signal can be detected while influences ofuncertain factors are eliminated. The uncertain factors include thechange in influence of the scatterers on the photoacoustic signal by thechange in positional relationship between the photoacoustic signalgeneration source and the acoustic wave detection means as well as bythe change at the contact between the acoustic wave detection means andthe object to be measured. Therefore, the constituent concentration canbe measured with no influence of the many parameters associated with thepositional change of the constituent concentration measuring apparatus.

In searching the optimal arrangement of the devices in terms of theobject to be measured in a measuring system by the photoacoustic method,means for adjusting the arrangement is mechanized to operateconcurrently with the acoustic wave detection means, which allows theconstituent concentration measurement to be automated to operate alwaysunder the optimum arrangement. In the invention, the intensity modulatedlight which is modulated by the constant frequency is used as theexcitation light.

According to one aspect of the invention, the influence of thereflecting/scattering scatterers on the photoacoustic signal is probedin each propagation path by changing the acoustic wave propagation path,and then the photoacoustic signal is detected by outputting theintensity modulated light such that the photoacoustic signal propagatesthrough the propagation path in which the acoustic wave intensitydetected by the acoustic wave detection means becomes the particularvalue. Therefore, the photoacoustic signal can be detected in theoptimum arrangement.

A constituent concentration measuring apparatus controlling methodaccording to one aspect of the invention is characterized bysequentially comprising a light generating procedure in which lightgenerating means generates two light beams having mutually differentwavelengths; a light modulation procedure in which light modulationmeans electrically intensity-modulates each of the two light beamshaving the mutually different wavelengths using signals having the samefrequency and reverse phases, the two light beams being generated in thea light generating procedure; a light outgoing procedure in which lightoutgoing means outputs the two light beams having the mutually differentwavelengths to an object to be measured, the two light beams beingintensity-modulated in the light modulation procedure; and an acousticwave detection procedure in which acoustic wave detection means detectsan acoustic wave emitted from said object to be measured by the lightoutputted in said light outgoing procedure.

In one aspect of the invention, each of the two light beams having themutually different wavelengths is electrically intensity-modulated usingthe signals having the same frequency and reverse phases, so that theacoustic wave corresponding to each of the two light beams having themutually different wavelengths can be detected with no influence from afrequency dependence of the acoustic wave detection means.

One of the two light beams generates acoustic wave having the pressurecorresponding to the total absorption in the state where the constituentof the measuring object and water are mixed together in the object to bemeasured, and the other light beam generates the acoustic wave havingthe pressure originating only from the water occupying the large part ofthe object to be measured, so that the pressure of the acoustic wavegenerated only by the constituent of the measuring object is detectableas the difference between two acoustic waves. As a result, quantity ofthe constitute in the measuring object can be measured.

With the two acoustic wave pressures, one generated by one of the twolight beams corresponding to the total absorption in the state where theconstituent of the measuring object and water are mixed together in theobject to be measured, while another generated by the other light beamcorresponding only to the water occupying the large part of the objectto be measured, their frequencies are equal to each other and the phaseare reversed to each other, therefore, the pressures are superposed toeach other in the form of acoustic wave in the object to be measured,and the difference in pressure of the acoustic waves is directlydetected. Accordingly, the difference in pressure of the acoustic wavescan be obtained more accurately rather than by computing the differencefrom separate measurements of the pressure of the acoustic wavegenerated by one of the two light beams corresponding to the totalabsorption in the state where the constituent of the measuring objectand water are mixed together in the object to be measured, as well as ofthe pressure of the acoustic wave generated by the other light beamcorresponding only to the water occupying the large part of the objectto be measured. The above point constitutes a novel advantage which doesnot exist in the conventional techniques.

In one aspect of the invention, the modulation frequency by which thetwo light beams having the mutually different wavelengths areelectrically intensity-modulated can be set to the resonant frequencyconcerning the detection of the acoustic wave generated in the object tobe measured. The photoacoustic signal is measured for the two lightbeams having mutually different wavelengths are selected by aconsideration on the non-linearity regarding to the absorptioncoefficient in the measured value of the photoacoustic signal. Then, theacoustic wave generated in the object to be measured can be measuredwith a high accuracy from the measured values while the influences ofthe many parameters which are hardly kept constant, are eliminated.

In the constituent concentration measuring apparatus controlling method,it is desirable to further comprise a frequency sweep procedure in whichfrequency sweep means sweeps a modulation frequency, the light generatedin the light generating procedure being modulated in the modulationfrequency; and an integration procedure in which integration meansintegrates the acoustic wave in a swept modulation frequency range, theacoustic wave being detected in the acoustic wave detection procedure.

In one aspect of the invention, the photoacoustic signal generated inthe object to be measured is integrated in the swept modulation signalrange. The photoacoustic signal exploiting the high sensitivity at thefrequency corresponding to the resonance frequency of the acoustic wavedetection means is integrated even if the resonance frequency of theacoustic wave detection means suffers a drift. Thus the measurement canbe performed always with the high-sensitivity resonance frequency.

In the constituent concentration measuring apparatus controlling method,it is desirable that the acoustic wave detection procedure is aprocedure in which the modulation frequency is tracked to detect theacoustic wave emitted in the said object to be measured by theirradiation light, the modulation frequency being swept in saidfrequency sweep procedure, and said integration procedure is a procedurein which the acoustic wave is integrated in the modulation frequencyrange where detection sensitivity of the acoustic wave is high in saidacoustic wave detection procedure, the acoustic wave being detected insaid acoustic wave detection procedure.

In one aspect of the invention, in the case where the resonancefrequency of the acoustic wave detection means happens to change, thechange in resonance frequency of the acoustic wave detection means inwhich the detection sensitivity becomes the maximum is determined fromthe result on the measurement of the photoacoustic signal generated bythe outputted light which is modulated by the frequency-swept modulationfrequency, and the change in resonance frequency is tracked to integratethe detected value of the photoacoustic signal near the resonancefrequency.

In the constituent concentration measuring apparatus controlling method,it is desirable to further comprise a liquid constituent concentrationcomputation procedure for computing a constituent concentration of aliquid constituent from the acoustic wave integrated in the integrationprocedure, the liquid constituent being set as a measuring object.

In one aspect of the invention, theoretical or experimental valuesshowing the relationship between the photoacoustic signal generated inthe object to be measured and the constituent concentration set as themeasuring object are prepared beforehand, and the constituentconcentration of the measuring object is computed based on the detectedvalue of the photoacoustic signal generated in the object to bemeasured.

In the constituent concentration measuring apparatus controlling methodit is desirable that the light outgoing procedure and said acoustic wavedetection procedure are performed in a container which is filled with anacoustic matching substance having an acoustic impedance substantiallyequal to that of the object to be measured.

By instituting the container filled with the acoustic matching substancehaving the acoustic impedance substantially equal to that of the objectto be measured, the object to be measured is arranged in the containerfilled with the acoustic matching substance having the acousticimpedance substantially equal to that of the object to be measured, andthe photoacoustic signal from the object to be measured can be detectedunder the environment in which the object to be measured is surroundedby the acoustic matching substance. This configuration leads to analleviation of the attenuation which is caused by the reflection of thephotoacoustic signal at the boundary between the object to be measuredand the surroundings as well as at the contact between the object to bemeasured and the acoustic wave detection means.

In the constituent concentration measuring apparatus controlling method,it is desirable that, in the acoustic wave detection procedure, saidacoustic wave is detected through an acoustic matching substance havingan acoustic impedance substantially equal to that of said object to bemeasured.

The photoacoustic signal is detected through the acoustic matchingsubstance having acoustic impedance substantially equal to that of theobject to be measured, so that the boundary reflection between theobject to be measured and the surroundings thereof and the pressure andvibration impairing the acoustic wave detection means can be prevented.

In the constituent concentration measuring apparatus controlling method,it is desirable that, in the light outgoing procedure, said intensitymodulated light is arranged on the inner wall of said container, andsaid intensity modulated light is outputted to said object to bemeasured through an outgoing window which is transparent for saidintensity modulated light.

The light outgoing means can be arranged outside the container furnishedwith the outgoing window transparent for the intensity modulated light,so that the light outgoing means is easily placed. The intensitymodulated light can be outputted from the inner wall surface of thecontainer, so that the influence of surface irregularity on the innerwall of the container to be suppressed to decrease the reflection of thephotoacoustic signal.

In the constituent concentration measuring apparatus controlling method,it is desirable that, in the object to be measured, a region irradiatedwith said intensity modulated light is covered with said acousticmatching substance in either sol or gel form.

In the object to be measured, the region irradiated with the intensitymodulated light is covered with the liquid, sol or gel acoustic matchingsubstance. Therefore, the photoacoustic signal can be detected from theobject to be measured under the environment in which the object to bemeasured is surrounded by the acoustic matching substance.

In the constituent concentration measuring apparatus controlling method,the constituent concentration measuring apparatus controlling methodfurther comprises an optimum position detection procedure in whichacoustic wave generators output acoustic waves from two or moredifferent positions to said object to be measured and acoustic wavedetection means detects a position where intensity of said acoustic wavetransmitted through said object to be measured becomes a particularvalue, the constituent concentration measuring apparatus controllingmethod characterized in that said light outgoing means outputs intensitymodulated light to said object to be measured from the position whereintensity of said acoustic wave becomes the particular value.

According to one aspect of the invention, the influence of thereflecting/scattering scatterers on the photoacoustic signal is probedin each propagation path by changing the acoustic wave propagation path,and then the photoacoustic signal is detected by outputting theintensity modulated light such that the photoacoustic signal propagatesthrough the propagation path in which the acoustic wave intensitydetected by the acoustic wave detection means becomes the particularvalue. Therefore, the photoacoustic signal can be detected in theoptimum arrangement.

In the constituent concentration measuring apparatus controlling method,it is desirable that the light generating procedure is a procedure forsetting the light wavelengths of said two light beams to two lightwavelengths where an absorption difference exhibited by the liquidconstituent set as the measuring object is larger than the absorptiondifference exhibited by a solvent.

In the constituent concentration measuring apparatus controlling method,it is desirable that the light generating procedure is a procedure forsetting one of the light wavelengths of said two light beams to a lightwavelength where the liquid constituent set as the measuring objectexhibits characteristic absorption, and while the other light wavelengthis set to a wavelength where the solvent exhibits an equal absorption tothat for said one of the light wavelengths.

One aspect of the invention is the case where the difference inabsorption exhibited by the solvent is set to zero, in the lightgenerating procedure in the constituent concentration measuringapparatus controlling method in which the light wavelengths of the twolight beams are set to two light wavelengths so that the absorptiondifference exhibited by the liquid constituent set as the measuringobject is larger than the absorption difference exhibited by thesolvent. Therefore, the influence by the absorption of the solvent canbe eliminated.

In the constituent concentration measuring apparatus controlling method,it is desirable that the light generating procedure is a procedure inwhich the light wavelengths of said two light beams are set to twowavelengths where an absorption difference exhibited by the liquidconstituent set as the measuring object is larger than the absorptiondifference exhibited by other liquid constituents.

In the constituent concentration measuring apparatus controlling method,it is desirable that the two light beams from said light outgoing meansare combined and outputted to said object to be measured.

The light can be focused on the measurement region, so that thephotoacoustic signal can efficiently be generated.

In the constituent concentration measuring apparatus controlling method,it is desirable that the detected acoustic wave is further rectified andamplified to detect amplitude of the acoustic wave.

The amplitude of the ultrasonic wave can be detected from the detectedphotoacoustic signal.

In the constituent concentration measuring apparatus controlling method,it is desirable to further comprise a liquid constituent concentrationcomputation procedure for computing a constituent concentration of aliquid constituent from pressure of the acoustic wave detected in saidacoustic wave detection procedure, the liquid constituent being set as ameasuring object.

In the constituent concentration measuring apparatus controlling method,it is desirable to further comprise a recording procedure for recordingthe acoustic wave as a function of the modulation frequency after saidacoustic wave detection procedure, the acoustic wave being detected insaid acoustic wave detection procedure.

By including the means for recording the photoacoustic signal detectedby the acoustic wave detection means for each swept modulationfrequency, if resonance frequency of the acoustic wave detection meanshappens to change, still the modulation frequency sweep range of theirradiating light covers the range in which the resonance frequencypossibly changes, the values measured with high accuracy can be selectedfrom the detected photoacoustic signals, which are integrated andaveraged to confirm that the constituent concentration is correctlymeasured.

In the constituent concentration measuring apparatus controlling method,it is desirable that, in the light outgoing procedure, an object to bemeasured is placed in contact with an outgoing surface of said intensitymodulated light, and said object to be measured is directly irradiatedwith said intensity modulated light.

The object to be measured is arranged so as to come into contact withthe outgoing surface of the intensity modulated light, and the object tobe measured is directly irradiated with the intensity modulated light.Thus, the attenuation of intensity modulated light caused by theabsorption in the acoustic matching substance and the like can beprevented. Accordingly, since the object to be measured can efficientlybe irradiated with the intensity modulated light, the photoacousticsignal emitted from the object to be measured is increased, and theaccuracy can further be improved in the photoacoustic signal detected bythe acoustic wave detection means.

A constituent concentration measuring apparatus controlling methodaccording to one aspect of the invention is characterized bysequentially comprising a light generating procedure in which lightgenerating means generates light; a frequency sweep procedure in whichfrequency sweep means sweeps a modulation frequency, the light generatedin said light generating procedure being modulated in the modulationfrequency; a light modulation procedure in which light modulation meanselectrically intensity-modulates the light using a signal swept in saidfrequency sweep procedure, the light being generated in said lightgenerating procedure; a light outgoing procedure in which light outgoingmeans outputs the light intensity-modulated in said light modulationprocedure; an acoustic wave detection procedure in which acoustic wavedetection means detects an acoustic wave which is generated by the lightemitted in said light outgoing procedure; and an integration procedurein which integration means integrates the acoustic wave in a sweptmodulation frequency range, the acoustic wave being detected in saidacoustic wave detection procedure.

In one aspect of the invention, the light is electricallyintensity-modulated using the modulation signal whose frequency is sweptin a predetermined range, the intensity-modulated light is outputted,the photoacoustic signal generated by the outputted light is detected,and the detected photoacoustic signal is integrated to compute theconstituent concentration which is the measurement objective in the testsubject. At this point, the wavelength of the outputted light is set atthe wavelength in which the constituent set as the measuring objectexhibits the absorption. Thus, the change in sensitivity characteristicsof the acoustic wave detection means can be tracked to measure theconstituent concentration which is the measurement objective at thefrequency where the optimal sensitivity is attainable.

A constituent concentration measuring apparatus controlling methodaccording to one aspect of the invention comprising a light generatingprocedure in which light generating means generates light; a lightmodulation procedure in which light modulation means electricallyintensity-modulates the light at a constant frequency, the light beinggenerated in said light generating procedure; a light outgoing procedurein which light outgoing means outputs the intensity modulated lightintensity-modulated in said light modulation procedure; and an acousticwave detection procedure in which acoustic wave detection means detectsan acoustic wave generated by said intensity modulated light in saidlight outgoing procedure, the constituent concentration measuringapparatus controlling method characterized in that said light outgoingprocedure and said acoustic wave detection procedure are performed in acontainer filled with an acoustic matching substance having an acousticimpedance substantially equal to that of a test subject.

One aspect of the invention is characterized in that the photoacousticsignal is detected under the environment whose photoacoustic signal issubstantially equal to the acoustic impedance of the test subject. Theintensity modulated light which is intensity-modulated in the constantfrequency is outputted, the photoacoustic signal which is of theacoustic wave generated by the outputted light is detected to measurethe concentration of the particular constituent contained in the liquidby the acoustic wave detection means though the acoustic matchingsubstance. The light outgoing procedure and the acoustic wave detectionprocedure are performed in the container which is filled with theacoustic matching substance having an acoustic impedance substantiallyequal to that of the test subject. Therefore, the photoacoustic signalcan be detected under the environment in which the test subject issurrounded by the acoustic matching substance, and the attenuation canbe decreased. The attenuation is caused by the reflection ofphotoacoustic signal on the boundary between the test subject andsurroundings, and the attenuation also occurs at the contact between thetest subject and the acoustic wave detection means.

A constituent concentration measuring apparatus controlling methodaccording to one aspect of the invention is characterized bysequentially comprising an optimum position detection procedure in whichacoustic wave generators output acoustic waves from two or moredifferent positions to a test subject and acoustic wave detection meansdetects a position where intensity of said acoustic wave transmittedthrough said test subject becomes a particular value; and an acousticwave detection procedure in which light outgoing means outputs intensitymodulated light from the position where intensity of said acoustic wavetransmitted through said test subject becomes the particular value, theintensity modulated light being intensity-modulated at a constantfrequency, and said acoustic wave detection means detects the acousticwave emitted by said intensity modulated light.

One aspect of the invention is characterized in that, when theconstituent concentration which is the measurement objective is measuredby the photoacoustic method, the ultrasonic wave (in this case, referredto as acoustic wave) emitted from the acoustic wave generator which isplaced near irradiation position of the excitation light, i.e., nearsource of photoacoustic signal is detected as a reference signal tosearch for a arrangement which optimizes a positional relationshipbetween the photoacoustic signal source and the acoustic wave detectionmeans. The photoacoustic signal is detected under the optimumarrangement, which allows the constituent concentration to be measuredusing a propagation path which minimizes the adverse influence ofscatterers such as a bone.

When the photoacoustic signal is detected in the arrangement in whichthe detected acoustic wave signal intensity becomes a predeterminedvalue such that the attenuation amount of acoustic wave is keptconstant, the photoacoustic signal can be detected while influences ofuncertain factors are eliminated. The uncertain factors include thechange in influence of the scatterers on the photoacoustic signal by thechange in positional relationship between the photoacoustic signalgeneration source and the acoustic wave detection means as well as bythe change at the contact between the acoustic wave detection means andthe test subject. Therefore, the constituent concentration can bemeasured with no influence of the many parameters associated with thepositional change of the constituent concentration measuring apparatus.

When the test subject, particularly the living body and the devices areoptimally arranged in a measuring system of the photoacoustic method,means for adjusting the arrangement is mechanized to operateconcurrently with the acoustic wave detection means, which becomes theconstituent concentration measurement to be automated in the optimumarrangement. In the invention, the intensity modulated light which ismodulated by the constant frequency is used as the excitation light.

According to one aspect of the invention, the influence of thereflecting/scattering scatterers on the photoacoustic signal is probedin each propagation path by changing the acoustic wave propagation path,and then the photoacoustic signal is detected by outputting theintensity modulated light such that the photoacoustic signal propagatesthrough the path in which the acoustic wave intensity detected by theacoustic wave detection means becomes the particular value. Therefore,the photoacoustic signal can be detected in the optimum arrangement.

A constituent concentration measuring apparatus controlling methodaccording to one aspect of the invention is characterized bysequentially comprising a light generating procedure in which lightgenerating means generates two light beams having different wavelengths;a light modulation procedure in which light modulation meanselectrically intensity-modulates each of the two light beams having themutually different wavelengths using signals having the same frequencyand reverse phases, the two light beams having the mutually differentwavelengths being generated in said light generating procedure;

a light outgoing procedure in which light outgoing means outputs the twointensity-modulated light beams having the mutually differentwavelengths, which are intensity-modulated in said light modulationprocedure; and an acoustic wave detection procedure in which acousticwave detection means detects an acoustic wave generated by the lightemitted in said light outgoing procedure.

In one aspect of the invention, each of the two light beams having themutually different wavelengths is electrically intensity-modulated usingthe signals having the same frequency and reverse phases, so that theacoustic wave corresponding to each of the two light beams having themutually different wavelengths can be detected with no influence from afrequency dependence of the acoustic wave detection means.

One of the two light beams generates acoustic wave having the pressurecorresponding to the total absorption in the state where the constituentof the measuring object and water are mixed together in the testsubject, and the other light beam generates the acoustic wave having thepressure originating only from the water occupying the large part of thetest subject so that the pressure of the acoustic wave generated only bythe constituent of the measuring object is detectable as the differencebetween two acoustic waves. As a result, quantity of the constitute inthe measuring object can be measured.

With the two acoustic wave pressures, one generated by one of the twolight beams corresponding to the total absorption in the state where theconstituent of the measuring object and water are mixed together in thetest subject to be measured, while another generated by the other lightbeam corresponding only to the water occupying the large part of thetest subject to be measured, their frequencies are equal to each otherand the phase are reversed to each other, therefore, the pressures aresuperposed to each other in the form of acoustic wave in the testsubject, and the difference in pressure of the acoustic waves isdirectly detected. Accordingly, the difference in pressure of theacoustic waves can be obtained more accurately rather than by computingthe difference from separate measurement of the pressure of the acousticwave generated by one of the two light beams corresponding to the totalabsorption in the state where the constituent of the measuring objectand water are mixed together in the test subject to be measured, as wellas of the pressure of the acoustic wave generated by the other lightbeam corresponding only to the water occupying the large part of thetest subject. The above point constitutes a novel advantage which doesnot exist in the conventional techniques.

In one aspect of the invention, the modulation frequency by which thetwo light beams having the mutually different wavelengths areelectrically intensity-modulated can be set to the resonant frequencyconcerning the detection of the acoustic wave generated in the testsubject to be measured. The photoacoustic signal is measured for the twolight beams having mutually different wavelengths which are selected bya consideration on the non-linearity regarding to the absorptioncoefficient in the measured value of the photoacoustic signal. Then, theacoustic wave generated in the test subject can be measured with a highaccuracy from the measured values while the influences of the manyparameters which are hardly kept constant, are eliminated.

In the constituent concentration measuring apparatus controlling method,the constituent concentration measuring apparatus controlling methodfurther comprises a second light outgoing procedure in which secondlight outgoing means outputs the light intermittently emitted atintervals which are longer than the repetition period for said samefrequency, the constituent concentration measuring apparatus controllingmethod characterized in that, in said acoustic wave detection procedure,said acoustic wave detection means detects the acoustic wave generatedby the light beams outputted in said light outgoing procedure and saidsecond light outgoing procedure.

According to one aspect of the invention, the photoacoustic signalemission amount by the absorption at the constituent set as themeasuring object is increased in the test subject, particularly in theliving body tissue, so that the accurate constituent concentration canbe measured in the noninvasive manner.

In the constituent concentration measuring apparatus controlling method,it is desirable that the second light outgoing means outputs the lighthaving a wavelength which exhibits a characteristic absorption of aconstituent different from the constituent set as the measuring object.

Only the photoacoustic signal from the blood constituent can beincreased by raising the temperature of the blood tissue as comparedwith the non-blood tissue.

In the constituent concentration measuring apparatus controlling method,it is desirable that the second light outgoing means emits the lighthaving a wavelength which exhibits a characteristic absorption ofhemoglobin in blood.

Only the photoacoustic signal from the blood containing the hemoglobincan be increased by raising the temperature of the hemoglobin.

In the constituent concentration measuring apparatus controlling method,it is desirable that the second light outgoing means emits the light atintervals during which temperature rise of 2° C. or less is resulted inthe test subject.

The influence on the test subject can be suppressed to the minimum.

In the constituent concentration measuring apparatus controlling method,it is desirable that the second light outgoing means emits the light ofan intensity by which temperature rise of 2° C. or less is resulted inthe test subject.

The influence on the test subject can be suppressed to the minimum.

In the constituent concentration measuring apparatus controlling method,it is desirable to further comprise a frequency sweep procedure in whichfrequency sweep means sweeps a modulation frequency, the light generatedin said light generating procedure being modulated in the modulationfrequency; and an integration procedure in which integration meansintegrates the acoustic wave in a swept modulation frequency range, theacoustic wave being detected in said acoustic wave detection procedure.

In one aspect of the invention, the photoacoustic signal generated inthe test subject is integrated in the swept modulation signal range. Thephotoacoustic signal exploiting the high sensitivity in the frequencycorresponding to the resonance frequency of the acoustic wave detectionmeans is integrated even if the resonance frequency of the acoustic wavedetection means suffers a drift. Thus measurement can be performedalways with the high-sensitivity resonance frequency.

In the constituent concentration measuring apparatus controlling method,it is desirable that, in the acoustic wave detection procedure, themodulation frequency swept in said frequency sweep procedure is trackedto detect the acoustic wave emitted by the irradiated light, and in saidintegration procedure, the acoustic wave is integrated in the modulationfrequency range having high detection sensitivity in said acoustic wavedetection procedure, the acoustic wave being detected by said acousticwave detection procedure.

In one aspect of the invention, in the case where the resonancefrequency of the acoustic wave detection means happens to change, thechange in resonance frequency of the acoustic wave detection means inwhich the detection sensitivity becomes the maximum is determined fromthe result on the measurement of the photoacoustic signal emitted in thetest subject to be measured by the irradiation light which is modulatedby the frequency-swept modulation frequency, and the change in resonancefrequency is tracked to integrate the detected value of thephotoacoustic signal near the resonance frequency.

In the constituent concentration measuring apparatus controlling method,it is desirable to further comprise a constituent concentrationcomputation procedure for computing a constituent concentration of aconstituent from the acoustic wave integrated by said integrationprocedure, the constituent being set as a measuring object.

In one aspect of the invention, theoretical or experimental valuesshowing the relationship between the photoacoustic signal generated inthe test subject and the constituent concentration set as the measuringobject are prepared beforehand, and the constituent concentration of themeasuring object is computed based on the detected value of thephotoacoustic signal generated in the test subject.

In the constituent concentration measuring apparatus controlling method,it is desirable that the light outgoing procedure and said acoustic wavedetection procedure are performed in a container which is filled with anacoustic matching substance having an acoustic impedance substantiallyequal to that of a test subject.

The light outgoing procedure and the acoustic wave detection procedureare performed in the container filled with the acoustic matchingsubstance having an acoustic impedance substantially equal to that ofthe test subject, which allows the photoacoustic signal to be detectedunder the environment in which the test subject is surrounded by theacoustic matching substance. Therefore, the degradation of thephotoacoustic signal can be reduced. The degradation of thephotoacoustic signal is caused by the boundary reflection between thetest subject and the surrounding thereof as well as at the contactbetween the test subject and the acoustic wave detection means.

In the constituent concentration measuring apparatus controlling method,it is desirable that, in the acoustic wave detection procedure, saidacoustic wave is detected through an acoustic matching substance havingan acoustic impedance substantially equal to that of said test subject.

The photoacoustic signal is detected through the acoustic matchingsubstance having acoustic impedance substantially equal to that of thetest subject; so that the boundary reflection between the test subjectand the surroundings thereof and the pressure and vibration impairingthe acoustic wave detection means can be prevented.

In the constituent concentration measuring apparatus controlling method,it is desirable that, in the light outgoing procedure, said intensitymodulated light is arranged on the inner wall surface of said container,and said intensity modulated light is outputted through an outgoingwindow which is transparent for said intensity modulated light.

The light outgoing means can be arranged outside the container by beingfurnished with an outgoing window transparent for the intensitymodulated light in the container, so that the light outgoing means iseasily placed. The intensity modulated light can be outputted from theinner wall surface of the container, so that the influence of surfaceirregularity on the inner wall of the container can be suppressed todecrease the reflection of the photoacoustic signal.

In the constituent concentration measuring apparatus controlling method,it is desirable that, in the test subject, a region irradiated with saidintensity modulated light is covered with said acoustic matchingsubstance in either sol or gel form.

In the test subject, the region irradiated with the intensity modulatedlight is covered with the liquid, sol or gel acoustic matchingsubstance. Therefore, the photoacoustic signal can be detected from thetest subject under the environment in which the test subject issurrounded by the acoustic matching substance.

In the constituent concentration measuring apparatus controlling method,it is desirable that the container is filled with water as for saidacoustic matching substance.

Because the acoustic impedance of the test subject is very close to thatof the water, a detection of the photoacoustic signal under theenvironment where the test subject is surrounded by the water candecrease the attenuation of the photoacoustic signal due to thereflection which is caused by the boundary reflection between the testsubject and the surroundings and by the contact between the test subjectand the acoustic wave detection means.

In the constituent concentration measuring apparatus controlling method,it is desirable to further comprise an optimum position detectionprocedure in which acoustic wave generators output acoustic waves fromtwo or more different positions and acoustic wave detection meansdetects a position where intensity of said acoustic wave transmittedthrough said test subject becomes a particular value.

According to one aspect of the invention, the influence of thereflecting/scattering scatterers on the photoacoustic signal can beprobed for each propagation path by changing the acoustic wavepropagation path.

In the constituent concentration measuring apparatus controlling method,it is desirable that, the light outgoing means output the light from theposition where intensity of the acoustic wave becomes the particularvalue.

The photoacoustic signal can be detected under the optimum arrangementby outputting the intensity modulated light such that the photoacousticsignal propagates through the propagation path in which the acousticwave intensity detected by the acoustic wave detection means becomes theparticular value. Additionally the photoacoustic signal can always bedetected in the optimum arrangement by keeping the optimum positiondetection means to operate automatically on the light outgoing means.

In the constituent concentration measuring apparatus controlling method,it is desirable that, in the acoustic wave detection procedure, saidlight outgoing means emits the light through a transmission windowfurnished in a part of said acoustic wave generator, the transmissionwindow being transparent for said intensity modulated light.

According to one aspect of the invention, the test subject can beirradiated with the intensity modulated light through the acoustic wavegenerator. Therefore, the test subject can be irradiated with theintensity modulated light from the optimum position of the acoustic wavegenerator.

In the constituent concentration measuring apparatus controlling method,it is desirable that, in the optimum position detection procedure, saidacoustic wave generator outputs said acoustic wave having thesubstantially the same frequency as said intensity modulated light, orsaid acoustic wave generator increases or decreases the intensity of theacoustic wave outputted according to the intensity of said acoustic wavedetected in said acoustic wave detection means.

According to one aspect of the invention, the influence of thescatterers on the photoacoustic signal can be probed with the acousticwave having the frequency equal to that of the photoacoustic signaldetected by the acoustic wave detection means. The intensity of theacoustic wave outputted from the acoustic wave generator can beincreased or decreased according to the intensity of the acoustic wavedetected by the acoustic wave detection means, so that the detectedintensity can be compared even if the intensity detected by the acousticwave detection means is small.

In the constituent concentration measuring apparatus controlling method,it is desirable that, in the optimum position detection procedure, theacoustic wave generator and the acoustic wave detection means detect theacoustic wave by pressing the acoustic wave generator and the acousticwave detection means against the test subject with pressing force whosepressure can be controlled.

According to one aspect of the invention, since the pressure forpressing the acoustic wave generator and the acoustic wave detectionmeans against the test subject is controllable, the pressure at whichthe acoustic wave generator and the acoustic wave detection means comeinto contact with the test subject can be kept at a predetermined value.Therefore, the influence of the pressure on the test subject can bereduced.

In the constituent concentration measuring apparatus controlling method,it is desirable that the light generating procedure is a procedure inwhich the light wavelengths of said two light beams to two wavelengthswhere an absorption difference exhibited by the constituent set as ameasuring object is larger than the absorption difference exhibited by asolvent.

In the constituent concentration measuring apparatus controlling method,it is desirable that the light generating procedure is a procedure forsetting one of the light wavelengths of said two light beams is set to awavelength where the constituent set as the measuring object exhibitscharacteristic absorption while the other light wavelength is set to awavelength in which the solvent exhibits an equal absorption to that forsaid one of the light wavelengths.

One aspect of the invention is the case where the difference inabsorption exhibited by the solvent is set to zero, in the lightgenerating procedure in the constituent concentration measuringapparatus controlling method in which the light wavelengths of the twolight beams are set to two light wavelengths so that the absorptiondifference exhibited by the constituent set as the measuring object islarger than the absorption difference exhibited by the solvent. Thereby,the influence by the absorption of the solvent can be eliminated.

In the constituent concentration measuring apparatus controlling method,it is desirable that the light generating procedure is a procedure inwhich the light wavelengths of said two light beams are set to twowavelengths where an absorption difference exhibited by the liquidconstituent set as the measuring object is larger than the absorptiondifference exhibited by other liquid constituents.

In the constituent concentration measuring apparatus controlling method,it is desirable that the light generating procedure is a procedure forsetting the light wavelengths of said two light beams to two wavelengthswhere an absorption difference exhibited by the blood constituent set asthe measuring object is larger than the absorption difference exhibitedby a water.

In the constituent concentration measuring apparatus controlling method,it is desirable that the light generating procedure is a procedure forsetting one of the light wavelengths of said two light beams to a lightwavelength where the blood constituent set as the measuring objectexhibits characteristic absorption while the other light wavelength isset to a wavelength where a water exhibits an equal absorption to thatfor said one of the light wavelengths.

One aspect of the invention is the case where the difference inabsorption exhibited by the water is set to zero, in the lightgenerating procedure in the constituent concentration measuringapparatus in which the light wavelengths of the two light beams are setto two light wavelengths so that the absorption difference exhibited bythe blood constituent set as the measuring object is larger than theabsorption difference exhibited by the water. Therefore, the influenceby the absorption of the water can be eliminated.

In the constituent concentration measuring apparatus controlling method,it is desirable that the light generating procedure is a procedure forsetting the light wavelengths of said two light beams to two wavelengthswhere an absorption difference exhibited by the blood constituent set asthe measuring object is larger than the absorption difference exhibitedby other blood constituents.

In the constituent concentration measuring apparatus controlling method,it is desirable that the two light beams are combined and irradiatedfrom said light outgoing means.

The light can be focused on the measurement region, so that thephotoacoustic signal can efficiently be generated.

In the constituent concentration measuring apparatus controlling method,it is desirable that the detected acoustic wave is further rectified andamplified to detect amplitude of the acoustic wave.

The amplitude of the acoustic wave can be detected from the detectedphotoacoustic signal.

In the constituent concentration measuring apparatus controlling method,it is desirable that the rectifying amplification is phase sensitiveamplification.

The amplitude of the ultrasonic wave can be detected from thephotoacoustic signal with a high sensitivity.

In the constituent concentration measuring apparatus controlling method,it is desirable that diameters of the two light beams from said lightoutgoing means are substantially equal to each other.

The measurement accuracy can be improved by matching the measurementregions.

In the constituent concentration measuring apparatus controlling method,it is desirable to further comprise a constituent concentrationcomputation procedure for computing the concentration of a constituentfrom pressure of the acoustic wave detected by said acoustic wavedetection, the constituent being set as a measuring object.

In the constituent concentration measuring apparatus controlling method,it is desirable that the constituent concentration computation procedureis a procedure for measuring pressure of the acoustic wave generated bysaid two light beams having the mutually different wavelengths, and thepressure of the generated acoustic wave is generated when one of saidtwo light beams is set to zero power, and then diving the pressure ofthe acoustic wave generated by said two light beams by the pressure ofthe acoustic wave generated when one of said two light beams is set tozero power.

As described above, the pressure of the acoustic wave generated byirradiating the test subject with the two light beams having themutually different wavelengths is detected as the difference between thepressure of the acoustic wave generated by one of the two light beamscorresponding to the total absorption in the state where the constituentof the measuring object and water are mixed together in the test subjectand the pressure of the acoustic wave generated by the other light beamcorresponding to the water alone occupying the large part of the testsubject. The constituent concentration can be measured by dividing thedifference by the acoustic wave pressure generated when one of the twolight beams is set to zero, i.e., the acoustic wave pressure generatedsolely by the water occupying the large part of the test subjectaccording to the later-mentioned formula (5).

In the constituent concentration measuring apparatus controlling method,it is desirable that the light modulation procedure is a procedure forperforming modulation with the same frequency as a resonant frequencyconcerning detection of the generated acoustic wave.

In one aspect of the invention, the modulation frequency by which thetwo light beams having the mutually different wavelengths areelectrically intensity-modulated is set to the same frequency as theresonant frequency concerning the detection of the acoustic wavegenerated in the test subject. Therefore, the acoustic wave generated inthe test subject can be measured with high accuracy.

In the constituent concentration measuring apparatus controlling method,it is desirable to further comprise an intensity adjustment procedurebetween said light modulation procedure and said light outgoingprocedure, the intensity adjustment procedure adjusting relativeintensity of said two light beams having the mutually differentwavelengths such that pressure of the acoustic wave becomes zero, theacoustic wave being generated by combining said two intensity-modulatedlight beams having the different wavelengths into a single light beam toirradiate water.

According to the above calibration, the relative intensity between thetwo light beams having the mutually different wavelengths can be setsuch that the intensity of the photoacoustic signal emitted from thewater occupying the large part of test subject is equalized for thewavelengths of two light beams. Consequently for the whole system formeasuring photoacoustic signal, the relative intensity between the twolight beams having the mutually different wavelengths can be calibratedto improve the measurement accuracy.

In the constituent concentration measuring apparatus controlling method,it is desirable that the acoustic wave detection procedure is aprocedure for synchronizing with said modulation frequency to detect theacoustic wave by phase sensitive detection.

The photoacoustic signal is detected by the phase-sensitive detectionsynchronized with the modulation frequency, so that the detection can beperformed with a high accuracy.

In the constituent concentration measuring apparatus controlling method,it is desirable that the light generating procedure and the lightmodulation procedure are a procedure for directly modulating each of thetwo semiconductor laser light sources using the rectangular-waveformsignals having the same frequency and reverse phases.

In one aspect of the invention, the two light beams having the mutuallydifferent wavelengths can be generated and at the same time be modulatedby using two directly-modulated semiconductor laser light sources drivenby rectangular-waveform signals having the same frequency and reversephases, so that the apparatus configuration can be simplified.

In the constituent concentration measuring apparatus controlling method,it is desirable that a blood constituent which is set as the measuringobject is glucose or cholesterol.

In the case where the concentration of glucose or cholesterol ismeasured, the measurement can accurately be performed by irradiating thetest subject with the light having the wavelength exhibiting thecharacteristic absorption.

In the constituent concentration measuring apparatus controlling method,it is desirable to further comprise a recording procedure after saidacoustic wave detection procedure, recording procedure recording theacoustic wave as a function of the modulation frequency, the acousticwave being detected by said acoustic wave detection procedure.

By including the means for recording the photoacoustic signal detectedby the acoustic wave detection means for each swept modulationfrequency, if the resonance frequency of the acoustic wave detectionmeans happens to change, still the modulation frequency sweep range ofthe irradiating light covers the range in which the resonance frequencypossibly changes, the values measured with high accuracy can be selectedfrom the detected photoacoustic signals, which are integrated andaveraged to confirm that the constituent concentration is correctlymeasured.

In the constituent concentration measuring apparatus controlling method,it is desirable that, in the light outgoing procedure, a test subject isplaced in contact with an outgoing surface of said intensity modulatedlight.

The test subject is arranged so as to come into contact with theoutgoing surface of the intensity modulated light, and the test subjectis directly irradiated with the intensity modulated light. Thus, theattenuation of intensity modulated light caused by the absorption in theacoustic matching substance and the like can be prevented. Accordingly,since the test subject can efficiently be irradiated with the intensitymodulated light, the photoacoustic signal emitted from the test subjectis increased, and the accuracy can further be improved in thephotoacoustic signal detected by the acoustic wave detection means.

Effect of the Invention

In the noninvasive constituent concentration measuring apparatus andconstituent concentration measuring apparatus controlling methodaccording to the invention, when the photoacoustic signal emittedfollowing irradiation of the liquid or the test subject with theintensity-modulated light is detected to measure the constituentconcentration, the modulation frequency at which the light isintensity-modulated is swept in a range where the acoustic wavedetection means possibly shows the resonant high sensitivity, and thephotoacoustic signal is measured at the frequency where the modulationfrequency matches the resonance frequency of the acoustic wave detectionmeans. Therefore, the constituent concentration set as the measuringobject can correctly be measured.

In the noninvasive constituent concentration measuring apparatus andconstituent concentration measuring apparatus controlling methodaccording to the invention, the two light beams having the mutuallydifferent wavelengths are intensity-modulated at the same frequency, theliquid or the test subject is irradiated with the intensity-modulatedlight beams to measure the photoacoustic signal generated in the liquidor the test subject. Therefore, the unevenness on the frequencycharacteristics of the acoustic wave detection means does not haveadverse influence. In addition, the modulation frequency at which thelight is intensity-modulated is swept in the range spanning theresonance frequency of the acoustic wave detection means which ispossibly changed, and the photoacoustic signal is measured at thefrequency which matches the resonance frequency of the acoustic wavedetection means. Therefore, the detection is hardly affected by theexternal influence, and the measurement can correctly be performed.

In the constituent concentration measuring apparatus and constituentconcentration measuring apparatus controlling method according to theinvention, the photoacoustic signal is detected under the environment ofthe acoustic impedance which is substantially equal to the acousticimpedance of the object to be measured or the test subject, so thatsignal attenuation can be minimized. The attenuation is caused by theboundary reflection between the test subject and the surroundingsthereof, as well as by the contact between the test subject and theacoustic wave detection means. Furthermore, the decrease in soundcollection efficiency of acoustic wave detection means and the decreasein accuracy of the photoacoustic signal can also be prevented.

According to the invention, the arrangement in which the positionalrelationship between the photoacoustic signal generation source and theacoustic wave detection means becomes optimum is searched for. Thus, theconstituent concentration can be measured by detecting the photoacousticsignal in the optimum arrangement in which the scatterers such as a bonehas little influence.

Furthermore, the photoacoustic signal is detected in the arrangement inwhich the signal intensity of the detected acoustic wave becomes thepredetermined value, so that the constituent concentration can bemeasured without influence of the many parameters associated with achange in placement of the constituent concentration measuringapparatus.

Furthermore, the influence of the pressure pressing the test subject isreduced by pressing the acoustic wave detection means against the testsubject with a constant pressure.

Accordingly, in the photoacoustic method, the influence of thereflection/scattering or the influence of the pressure pressing the testsubject can be reduced to improve the measurement accuracy of thephotoacoustic signal.

In the noninvasive constituent concentration measuring apparatus andconstituent concentration measuring apparatus controlling methodaccording to the invention, the two light beams having the mutuallydifferent wavelengths are selected in consideration of the non-linearityof the photoacoustic signal in respect to the absorption coefficient,the photoacoustic signals for the light beams are measured, and theconstituent concentration set as the measuring object can correctly becomputed while the influence of the many parameters which are hardlykept constant are eliminated.

In the constituent concentration measuring apparatus and constituentconcentration measuring apparatus controlling method according to theinvention, the two light beams having the mutually different wavelengthsare selected in consideration of the non-linearity of the photoacousticsignal in respect to the absorption coefficient, the photoacousticsignals, for the light beams are measured, and the constituentconcentration set as the measuring object can correctly be computedwhile the influence of the many parameters which are hardly keptconstant are eliminated. In the noninvasive constituent concentrationmeasuring apparatus and constituent concentration measuring apparatuscontrolling method according to the invention, the two light beamshaving the mutually different wavelengths are intensity-modulated by thesignals having the same frequency, the test subject is irradiated withthe intensity-modulated light beams to measure the photoacoustic signalgenerated in the test subject. Therefore, the unevenness on thefrequency characteristics of the acoustic wave detection means does notaffect the measurement. Furthermore, the invention enables anapplication of the resonance type detector which is effective for theimprovement of the acoustic wave detection sensitivity, and themeasurement can be performed in a short time even for physicallydebilitated persons or ambulatory animals. Furthermore, in theconstituent concentration measuring apparatus and constituentconcentration measuring apparatus controlling method according to theinvention, either the forward propagation type that detects the acousticwave propagating in the direction of irradiation or the backwardpropagation type that detects the acoustic wave propagating back to theirradiation can be configured. Particularly, the latter is convenientfor miniaturization.

In the constituent concentration measuring apparatus and constituentconcentration measuring apparatus controlling method according to theinvention, the constituent contained in the liquid can correctly bemeasured in the noninvasive manner. In the constituent concentrationmeasuring apparatus and constituent concentration measuring apparatuscontrolling method according to the invention, the test subject isirradiated with three light beams to measure the photoacoustic signalfrom the test subject. Thus, the constituent concentration contained inthe test subject can correctly be measured in the noninvasive manner.Particularly, the background signal from non-blood tissues can beremoved, when the third light wavelength is set at the wavelength inwhich the blood alone exhibits absorption.

In the noninvasive constituent concentration measuring apparatusaccording to the invention, the constituent concentration of the testsubject can be measured in the noninvasive manner. The size of the testsubject including its sides is kept constant, and moreover reflectedwave from those sides is suppressed. Therefore, the constituentconcentration can be measured stably and correctly. In the noninvasiveconstituent concentration measuring apparatus according to theinvention, the compact and contact apparatus can be realized by formingthe apparatus in the ring shape or the bracelet shape, and the apparatuscan be fitted while carried.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an explanatory view showing a configuration of a bloodconstituent concentration measuring apparatus according to anembodiment;

FIG. 2 is an explanatory view of a sound source distribution in a livingbody;

FIG. 3 is an explanatory view of a shape function for the sound sourcedistribution in the living body;

FIG. 4 is an explanatory view showing a photoacoustic signal of theblood constituent concentration measuring apparatus according to theembodiment;

FIG. 5 is an explanatory view showing the photoacoustic signal of theblood constituent concentration measuring apparatus according to theembodiment;

FIG. 6 is an explanatory view showing the photoacoustic signal of theblood constituent concentration measuring apparatus according to theembodiment;

FIG. 7 is an explanatory view showing a pair of wavelengths used alongwith the light absorption properties of water and glucose;

FIG. 8 is an explanatory view showing the light absorption properties ofwater and glucose;

FIG. 9 is an explanatory view showing a configuration example of theblood constituent concentration measuring apparatus according to theembodiment;

FIG. 10 is an explanatory view showing a configuration example of theblood constituent concentration measuring apparatus according to theembodiment;

FIG. 11 is an explanatory view showing the light absorption propertiesof water;

FIG. 12 is an explanatory view showing the light absorption propertiesof cholesterol;

FIG. 13 is an explanatory view showing a configuration example of theblood constituent concentration measuring apparatus according to theembodiment;

FIG. 14 is an explanatory view showing the embodiment of the bloodconstituent concentration measuring apparatus according to theembodiment;

FIG. 15 is an explanatory view showing the embodiment of the bloodconstituent concentration measuring apparatus according to theembodiment;

FIG. 16 is an explanatory view showing the photoacoustic signal in theembodiment;

FIG. 17 is an explanatory view showing the photoacoustic signal in theembodiment;

FIG. 18 is an explanatory view showing an example of the bloodconstituent concentration measuring apparatus according to theembodiment;

FIG. 19 is an explanatory view showing an example of the bloodconstituent concentration measuring apparatus according to theembodiment;

FIG. 20 is an explanatory view showing a configuration of the bloodconstituent concentration measuring apparatus according to theembodiment;

FIG. 21 is an explanatory view showing sensitivity characteristics of anultrasonic detector according to the embodiment;

FIG. 22 is an explanatory view showing a configuration of the bloodconstituent concentration measuring apparatus according to theembodiment;

FIG. 23 is a schematic view showing an example of the blood constituentconcentration measuring apparatus according to the embodiment;

FIG. 24 is a transverse sectional view taken on line D-D′ of FIG. 23,and FIG. 24 shows a first mode of the blood constituent concentrationmeasuring apparatus;

FIG. 25 is a transverse sectional view taken on line D-D′ of FIG. 23,and FIG. 25 shows a second mode of the blood constituent concentrationmeasuring apparatus;

FIG. 26 is a longitudinal sectional showing a fourth mode of the bloodconstituent concentration measuring apparatus;

FIG. 27 is a longitudinal sectional showing a fifth mode of the bloodconstituent concentration measuring apparatus;

FIG. 28 is a transverse sectional view taken on line F-F′ of FIG. 27;

FIG. 29 is a circuit diagram showing an example of the blood constituentconcentration measuring apparatus;

FIG. 30 is a longitudinal sectional view of the blood constituentconcentration measuring apparatus, and FIG. 30 shows an example in whichthe blood constituent concentration measuring apparatus is applied to afingertip of a human body;

FIG. 31 is a transverse sectional view taken on line H-H′ of FIG. 30;

FIG. 32 is a longitudinal sectional view of the blood constituentconcentration measuring apparatus, and FIG. 32 shows an example in whichthe blood constituent concentration measuring apparatus is applied tothe finger of the human body;

FIG. 33 is a transverse sectional view taken on line N-N′ of FIG. 32;

FIG. 34 is a circuit diagram of the blood constituent concentrationmeasuring apparatus according to the embodiment;

FIG. 35 is a schematic view showing an example of an acoustic wavegenerator and acoustic wave detection means, FIG. 35( a) is an externalview, FIG. 35( b) is a top view of the acoustic wave generator, FIG. 35(c) is a perspective view of the acoustic wave generator, and FIG. 35( d)is a bottom view of the acoustic wave generator;

FIG. 36 is a circuit diagram of the blood constituent concentrationmeasuring apparatus according to the embodiment;

FIG. 37 is an explanatory view showing a configuration of the bloodconstituent concentration measuring apparatus according to anembodiment;

FIG. 38 is an explanatory view showing the structure of an enduing unitof the blood constituent concentration measuring apparatus according tothe embodiment;

FIG. 39 is an explanatory view showing the structure of an enduing unitof the blood constituent concentration measuring apparatus according tothe embodiment;

FIG. 40 is an explanatory view showing a structure of an enduing unit ofthe blood constituent concentration measuring apparatus according to theembodiment;

FIG. 41 is an explanatory view of a ring type enduing unit according tothe embodiment;

FIG. 42 is an explanatory view showing a detailed structure of the ringtype enduing unit according to the embodiment;

FIG. 43 is an explanatory view showing a cross section of the ring typeenduing unit according to the embodiment;

FIG. 44 is an explanatory view of a ring type light generation unitaccording to the embodiment;

FIG. 45 is an explanatory view showing the cross section of the ringtype enduing unit according to the embodiment;

FIG. 46 is an explanatory view of a bracelet type enduing unit accordingto the embodiment;

FIG. 47 is an explanatory view of the bracelet type enduing unitaccording to the embodiment;

FIG. 48 is an explanatory view showing the cross section of the bracelettype enduing unit according to the embodiment;

FIG. 49 is an explanatory view showing a configuration example of aconventional blood constituent concentration measuring apparatus;

FIG. 50 is an explanatory view showing a configuration example of theconventional blood constituent concentration measuring apparatus;

FIG. 51 is an explanatory view of the conventional blood constituentconcentration measuring apparatus;

FIG. 52 is an explanatory view of a mounting structure of theconventional blood constituent concentration measuring apparatus;

FIG. 53 is an explanatory view showing the sensitivity characteristicsof the ultrasonic detector;

FIG. 54 is an explanatory view showing the sensitivity characteristicsof the ultrasonic detector;

FIG. 55 is a sectional view showing a inner structure of a finger;

FIG. 56 is a sectional view showing the human finger, FIG. 56( a) showsa state in which the photoacoustic signal is scattered by a bone, andFIG. 56( b) shows a state in which the photoacoustic signal isattenuated by the bone;

FIG. 57 is an explanatory view showing a configuration of the bloodconstituent concentration measuring apparatus according to theembodiment (addendum);

FIG. 58 is an explanatory view showing a computation principle of theblood constituent concentration measuring apparatus according to theembodiment (addendum);

FIG. 59 is an explanatory view showing the computation principle of theblood constituent concentration measuring apparatus according to theembodiment (addendum);

FIG. 60 is a view showing an example of the blood constituentconcentration measuring apparatus according to the embodiment(addendum); and

FIG. 61 is a view showing an example of the blood constituentconcentration measuring apparatus according to the embodiment(addendum).

DESCRIPTION OF THE REFERENCE NUMERALS

-   -   1 intensity modulated light    -   2 acoustic wave    -   3 photoacoustic signal    -   4 output signal    -   5 control signal    -   11 light generation unit    -   12 light modulation unit    -   13 light outgoing unit    -   14 ultrasonic detection unit    -   15 sound absorbing material    -   16 temperature measurement unit    -   17 outgoing window    -   18 reflection material    -   21 container    -   22 inside    -   23 excitation light source    -   24 acoustic wave generator    -   25 acoustic wave detector    -   26 control unit    -   27 drive unit    -   28 acoustic coupling element    -   29 transmission window    -   31 power supply    -   32 phase sensitive amplifier    -   33 signal processor    -   34 display processor    -   35 connection cable    -   36 temperature regulating unit    -   37 heater    -   38 preamplifier    -   39 light source chip    -   40 lens    -   41 beam splitter    -   42 optical fiber    -   51 oscillator    -   52 180°-phase shifter    -   53 drive circuit    -   55 coupler    -   56 acoustic matching substance    -   57 filter    -   58 phase sensitive amplifier    -   59 photoacoustic signal output, terminal    -   97 living body test region    -   99 lens    -   100 oscillator    -   101 first light source    -   102 drive circuit    -   103 oscillator    -   104 drive circuit    -   105 second light source    -   106 third light source    -   107 180°-phase-shift circuit    -   108 drive circuit    -   109 coupler    -   110 living body test region    -   111 living body test region    -   112 light source    -   113 ultrasonic detector    -   114 phase sensitive amplifier    -   115 output terminal    -   116 drive circuit    -   117 drive circuit    -   118 frequency divider    -   119 180°-phase shifter    -   120 coupler    -   121 ultrasonic detector    -   122 filter    -   123 synchronous detection amplifier    -   124 photoacoustic signal output terminal    -   125 control circuit    -   126 acoustic coupler    -   127 ultrasonic detector    -   128 phase sensitive amplifier    -   129 computing device    -   130 enduing unit    -   131 living body    -   132 annular support frame    -   133 light irradiation unit    -   135 ultrasonic detection unit    -   136 cushioning material    -   137 sound absorbing material    -   138 contact thermometer    -   139 lens    -   140 lens    -   141 calibration test sample    -   142 acoustic coupler    -   143 thermometer    -   193 living body    -   194 output waveform of first light source    -   195 output waveform of second light source    -   196 output waveform of third light source    -   197 photoacoustic signal by first light source    -   198 photoacoustic signal by second light source    -   199 temperature change by third light source    -   200 summation of photoacoustic signals    -   201 light irradiation    -   202 sound source    -   203 observation point    -   204 model A    -   205 model B    -   206 model C    -   207 enduing unit    -   208 Δs₁    -   209 Δs₂    -   210 connection cable    -   211 light from first light source (λ₁)    -   212 light from second light source (λ₂)    -   213 bone    -   214 muscle    -   215 fat    -   216 cuticle    -   217 reflecting location    -   218 blood vessel    -   219 excitation light    -   220 detector    -   221 display unit    -   222 frame    -   297 drive circuit    -   298 oscillator    -   299 180°-phase shifter    -   300 control circuit    -   301 first light source    -   302 second light source    -   303 drive circuit    -   304 irradiation light    -   305 ultrasonic detector    -   306 cushioning material    -   307 sound absorbing material    -   308 coupler    -   309 living body test region    -   310 connection cable    -   311 frame    -   312 preamplifier    -   313 irradiation window    -   314 light source chip    -   315 output beam    -   316 reflecting mirror    -   317 concave mirror    -   318 first semiconductor laser    -   319 second semiconductor laser    -   320 electrode pad    -   321 substrate    -   322 optical waveguide    -   323 coupler    -   324 vibration membrane    -   325 fixed electrode    -   326 wiring cavity    -   327 acoustic coupler    -   328 ultrasonic detector    -   329 phase sensitive amplifier    -   330 computing device    -   400 living body    -   401 semiconductor laser device    -   402 drive power supply    -   404 acoustic wave generator    -   405 test subject    -   403 oscillator    -   406 acoustic coupling element    -   407 acoustic wave detector    -   408 phase sensitive amplifier    -   409 output terminal    -   410 hole    -   413 irradiation window    -   414 light source, chip    -   415 output beam    -   416 reflecting mirror    -   417 irradiation light    -   418 cushioning material    -   419 display unit    -   421 light irradiation unit    -   428 wrist band    -   429 insertion key    -   430 opening    -   431 release button    -   432 lens    -   433 light sources chassis    -   499 living body    -   500 light source    -   501 first semiconductor light source    -   502 lens    -   503 oscillator    -   504 drive current source    -   505 second semiconductor light source    -   506 lens    -   507 180°-phase-shift circuit    -   508 drive current source    -   509 coupler    -   510 living body test region    -   511 calibration test sample    -   512 acoustic coupler    -   513 ultrasonic detector    -   514 phase sensitive amplifier    -   515 output terminal    -   516 acoustic lens    -   517 acoustic matching device    -   518 ultrasonic detector    -   519 high pass filter    -   520 synchronous detection amplifier    -   521 photoacoustic signal output terminal    -   522 temperature measurement device    -   523 first semiconductor light source    -   524 drive current source    -   525 oscillator    -   526 lens    -   527 second semiconductor light source    -   528 drive current source    -   529 180°-phase shifter    -   530 lens    -   531 coupler    -   532 third semiconductor light source    -   533 drive current source    -   534 frequency divider    -   535 lens    -   536 coupler    -   537 living body test region    -   540 apparatus body    -   541 acoustic wave detector    -   601 first light source    -   604 drive power supply    -   605 second light source    -   608 drive power supply    -   609 coupler    -   610 living body test region    -   613 ultrasonic detector    -   616 pulse light source    -   617 chopper plate    -   618 motor    -   619 acoustic sensor    -   620 waveform observing apparatus    -   621 frequency analyzer    -   701 first semiconductor light source    -   702 drive current source    -   703 oscillator    -   704 lens    -   705 second semiconductor light source    -   706 drive current source    -   707 180°-phase shifter    -   708 lens    -   709 coupler    -   710 third semiconductor light source    -   711 drive current source    -   712 frequency divider    -   713 lens    -   714 coupler    -   715 liquid sample    -   716 sample cell    -   717 acoustic matching device    -   718 ultrasonic detector    -   719 high pass filter    -   720 synchronous detection amplifier    -   721 photoacoustic signal output terminal    -   722 temperature measurement device    -   801 first semiconductor light source    -   802 lens    -   803 oscillator    -   804 drive current source    -   805 second semiconductor light source    -   806 lens    -   807 180°-phase-shift circuit    -   808 drive current source    -   809 coupler    -   810 living body test region    -   811 calibration specimen    -   812 acoustic coupler    -   813 ultrasonic detector    -   814 phase sensitive amplifier    -   815 output terminal

BEST MODE FOR CARRYING OUT THE INVENTION

Embodiments of the invention will be described below. The invention isnot limited to the following embodiments. In the following embodiments,the constituent concentration measuring apparatus and the constituentconcentration measuring apparatus controlling method are described inthe form of a blood constituent concentration measuring apparatus and acontrol method of blood constituent concentration measuring apparatus.However, when the living body which is of the test subject is replacedby the liquid which is of the object to be measured, when the bloodwhich is of the test subject is replaced by the liquid which is of theobject to be measured, and when the water is replaced by the liquidsolvent, the invention can be realizes as the liquid constituentconcentration measuring apparatus or the liquid constituentconcentration measuring apparatus controlling method. The test subjectis not limited to the living body and the blood. For example, “lymph”and “tear” are also included in the test subject. In the case where theliving body is used as the test subject, the constituent set as themeasuring object is not limited to the blood constituent, but theconstituent includes the constituents such as “lymph constituent” and“tear constituent”. Thus, in the invention, various constituents can bemeasured according to the measuring object.

First Embodiment

A constituent concentration measuring apparatus according to a firstembodiment is a blood constituent concentration measuring apparatusincluding light generating means for generating two light beams havingdifferent wavelengths; light modulation means for electricallyintensity-modulating each of the two light beams having the mutuallydifferent wavelengths using signals having the same frequency andreverse phases; light outgoing means for multiplexing the twointensity-modulated light beams having the mutually differentwavelengths into one light flux to output the light toward a livingbody; acoustic wave detection means for detecting an acoustic wavegenerated in the living body by the outputted light; and bloodconstituent concentration computation means for computing a bloodconstituent concentration in the living body from pressure of thedetected acoustic wave. The blood constituent concentration computationmeans according to the first embodiment is applied in the firstembodiment, and the blood constituent concentration computation meansaccording to the first embodiment can also be applied in thelater-mentioned second embodiment, third embodiment, fourth embodiment,fifth embodiment, and sixth embodiment.

In the blood constituent concentration measuring apparatus according tothe first embodiment, the light generating means can set one of thelight wavelengths of the two light beams at the wavelength in which theblood constituent exhibits the characteristic absorption, and the lightgenerating means can set the other light wavelength at the wavelength inwhich the water exhibits the absorption parallelly equal to that in oneof the light wavelengths.

A configuration according to the first embodiment will be described withreference to FIG. 1. FIG. 1 shows a basic configuration of a bloodconstituent concentration measuring apparatus according to the firstembodiment. In FIG. 1, a first light source 101 which is of a part ofthe light generating means is intensity-modulated in synchronizationwith an oscillator 103 which is of a part of the light modulation meansby a drive circuit 104 which is of a part of the light modulation means.

On the other hand, a second light source 105 which is of a part of thelight generating means is intensity-modulated in synchronization withthe oscillator 103 by a drive circuit 108 which is of a part of thelight modulation means. However, output of the oscillator 103 issupplied to the drive circuit 108 through a 180°-phase-shift circuit 107which is of a part of the light modulation means, and thereby the secondlight source 105 is configured so as to be intensity-modulated with thesignal whose phase is changed by 180° with respect to the first lightsource 101.

In the wavelengths of the first light source 101 and second light source105 shown in FIG. 1, the wavelength of one of the two light beams is setat the wavelength in which the blood constituent exhibits thecharacteristic absorption, and the wavelength of the other light beam isset at the wavelength in which the water exhibits the absorptionparallelly equal to that in the wavelength of one of the two lightbeams.

The first light source 101 and the second light source 105 output thelight beams having the different wavelengths respectively, the lightbeams are multiplexed as one light flux by a coupler 109 which is of thelight outgoing means, and a living body test region 110 which is of thetest subject is irradiated with the light. The acoustic waves, i.e.,photoacoustic signals generated in the living body test region 110 bythe light beams outputted from the first light source 101 and the secondlight source 105 are detected by an ultrasonic detector 113 which is ofthe acoustic wave detection means, and the photoacoustic signals areconverted into the electric signals proportional to the acousticpressure of the photoacoustic signals. The synchronous detection isperformed to the electric signal by a phase sensitive amplifier 114which is of a part of the acoustic wave detection means synchronizedwith the oscillator 103, and the electric signal proportional to theacoustic pressure is outputted to an output terminal 115.

The intensity of the signal outputted to the output terminal 115 isproportional to a light quantity in which the light beam outputted fromeach of the first light source 101 and second light source 105 isabsorbed by the constituent in the living body test region 110, so thatthe signal intensity is proportional to the mount of constituent in theliving body test region 110. Accordingly, the blood constituentconcentration computation means (not shown) computes the mount ofconstituent of the measuring object in the blood of the living body testregion 110 from the measured value of the intensity of the signaloutputted to the output terminal 115.

In the blood constituent concentration measuring apparatus according tothe first embodiment, the two light beams having different wavelengthsoutputted from the first light source 101 and second light source 105are intensity-modulated using the signals having the same period, i.e.,the same frequency. Therefore, the blood constituent concentrationmeasuring apparatus according to the first embodiment has a feature thatthe blood constituent concentration measuring apparatus according to thefirst embodiment is not affected by the unevenness of the frequencycharacteristics of the ultrasonic detector 113. This is the excellentpoint as compared with the currently existing techniques.

As described above, the blood constituent concentration measuringapparatus according to the first embodiment can measure the bloodconstituent with high accuracy.

The control method of blood constituent concentration measuringapparatus according to the first embodiment is a control method of bloodconstituent concentration measuring apparatus sequentially including alight generating procedure in which the light generating means generatesthe two light beams having mutually different wavelengths; a lightmodulation procedure in which the light modulation means electricallyintensity-modulates each of the two light beams having the mutuallydifferent wavelengths generated in the light generating procedure usingsignals having the same frequency and reverse phases; a light outgoingprocedure in which the light outgoing means multiplexes the twointensity-modulated light beams having the different wavelengthsintensity-modulated in the light modulation procedure into one lightflux to output the light toward the living body; an acoustic wavedetection procedure in which the acoustic wave detection means detectsthe acoustic wave generated in the living body by the light outputted inthe light outgoing procedure; and a constituent concentrationcomputation procedure in which the blood constituent concentration inthe living body is computed from pressure of the detected acoustic wave.The blood constituent concentration computation procedure according tothe first embodiment is applied in the first embodiment, and the bloodconstituent concentration computation procedure according to the firstembodiment can also be applied in the later-mentioned second embodiment,third embodiment, fourth embodiment, fifth embodiment, and sixthembodiment.

The control method of blood constituent concentration measuringapparatus according to the first embodiment can also be formed in acontrol method of blood constituent concentration measuring apparatus inwhich, in the light generating procedure, the wavelength of one of thetwo light beams is set at the wavelength in which the blood constituentexhibits the characteristic absorption, and the wavelength of the otherlight beam is set at the wavelength in which the water exhibits theabsorption parallelly equal to that in the wavelength of one of the twolight beams.

A method in which the two light beams having different wavelengths isgenerated and each of the two light beams having different wavelengthsis electrically intensity-modulates by a modulator using the signalshaving the same frequency and 180°-different phases may be adopted asthe method of electrically intensity-modulating each of the two lightbeams having different wavelengths. Alternately, as shown in FIG. 1, adirect modulation method in which the drive circuit 104 and the drivecircuit 108 cause the first light source 101 and the second light source105 to emit the light and simultaneously perform the intensitymodulation may be adopted as the method of electricallyintensity-modulating each of the two light beams having differentwavelengths.

The two light beams having different wavelengths intensity-modulatedthrough the above procedure are multiplexed into one light flux by thecoupler 109 shown in FIG. 9, the living body is irradiated with thelight, the acoustic waves, i.e., the photoacoustic signals generated inthe living body by the two light beams having different wavelengths withwhich the living body is irradiated are detected by the ultrasonicdetector 113 shown in FIG. 1, the detected photoacoustic signals areconverted into the electric signals, the electric signals aresynchronous-detected by the phase sensitive amplifier 114 shown in FIG.1, and the electric signals being proportional to the photoacousticsignals are outputted to the output terminal 115. Then, in the bloodconstituent concentration computation procedure, the blood constituentconcentration in the living body is computed from the pressure of theacoustic wave detected in the acoustic wave detection procedure.

In the control method of blood constituent concentration measuringapparatus according to the first embodiment, the two light beams havingdifferent wavelengths outputted from the first light source 101 andsecond light source 105 are intensity-modulated using the signals havingthe same period, i.e., the same frequency. Therefore, the control methodof blood constituent concentration measuring apparatus according to thefirst embodiment has a feature that the control method of bloodconstituent concentration measuring apparatus according to the firstembodiment is not affected by the unevenness of the frequencycharacteristics of the ultrasonic detector. This is the excellent pointas compared with the currently existing techniques.

As described above, the control method of blood constituentconcentration measuring apparatus according to the first embodiment canmeasure the blood constituent with high accuracy.

In the blood constituent concentration measuring apparatus according tothe first embodiment, the light modulation means can also be formed inmeans for performing the modulation with the same frequency as theresonant frequency concerning the detection of the acoustic wavegenerated in the living body. The light modulation means described inthe first embodiment is similar to those of the later-mentioned secondembodiment, third embodiment, fourth embodiment, fifth embodiment, andsixth embodiment.

The two light beams having different wavelengths is modulated with thesame frequency as the resonant frequency concerning the detection of theacoustic wave generated in the living body, which allows the acousticwave generated in the living body to be detected with high sensitivity.

In the control method of blood constituent concentration measuringapparatus according to the first embodiment, the light modulationprocedure can also be formed in a procedure of performing the modulationwith the same frequency as the resonant frequency concerning thedetection of the acoustic wave generated in the living body.

The two light beams having different wavelengths is modulated with thesame frequency as the resonant frequency concerning the detection of theacoustic wave generated in the living body, which allows the acousticwave generated in the living body to be detected with high sensitivity.

In the blood constituent concentration measuring apparatus according tothe first embodiment, the blood constituent concentration computationmeans can also be formed in means for dividing the pressure of theacoustic wave generated by irradiating the living body with the twolight beams having different wavelengths by the pressure of the acousticwave which is generated when one of the two light beams is set to zero.

The blood constituent concentration can be measured with high accuracyby the division.

In the control method of blood constituent concentration measuringapparatus according to the first embodiment, the blood constituentconcentration computation procedure can also formed in a procedure fordividing the pressure of the acoustic wave generated by irradiating theliving body with the two light beams by the pressure of the acousticwave which is generated when one of the two light beams is set to zero.

The blood constituent concentration can be measure with high accuracy bythe above division.

In the blood constituent concentration measuring apparatus according tothe first embodiment, the light generating means can be formed in meansfor adjusting the relative intensity of two light beams having thedifferent wavelengths such that the pressure of the acoustic wavebecomes zero. The pressure of the acoustic wave is generated byirradiating water with the two intensity-modulated light beams havingthe different wavelengths multiplexed into one light flux. The lightgenerating means described in the first embodiment is similar to thoseof the later-mentioned second embodiment, third embodiment, fourthembodiment, fifth embodiment, and sixth embodiment.

In the blood constituent concentration measuring apparatus according tothe first embodiment, for example, as shown in FIG. 1, as with themeasurement of the blood constituent concentration, the water forcalibration instead of the living body test region 110 is irradiatedwith one light flux into which are multiplexed, and the relativeintensity of the light beams outputted from the first light source 101and second light source 105 is adjusted such that the photoacousticsignal detected by the ultrasonic detector 113 becomes zero.

In adjusting the intensity of the light outputted from each of the firstlight source 101 and second light source 105 in the above-describedmanner, the relative intensity of each of two light beams outputted fromthe first light source 101 and second light source 105 can easilyequally be adjusted, so that the blood constituent concentration can bemeasured with high accuracy.

In the control method of blood constituent concentration measuringapparatus according to the first embodiment, control method of bloodconstituent concentration measuring apparatus can also further includean intensity adjustment procedure between the light modulation procedureand the light outgoing procedure. In the intensity adjustment procedure,the intensity-modulated two light beams having the different wavelengthsare multiplexed into one light flux, the water is irradiated with thelight, and the relative intensity of each of the two light beams isadjusted such that the pressure of the acoustic wave generated by theirradiation becomes zero.

In the control method of blood constituent concentration measuringapparatus according to the first embodiment, for example, after theprocedure of multiplexing the intensity-modulated two light beams havingthe different wavelengths into one light flux, the two light beamshaving the different wavelengths are multiplexed into one light flux,the light is outputted to the water, and the relative intensity of eachof the two light beams is adjusted such that the pressure of theacoustic wave generated by the irradiation becomes zero. Therefore, therelative intensity of each of the two light beams outputted from thefirst light source 101 and second light source 105 can easily equally beadjusted, so that the blood constituent can easily be measured.

In the blood constituent concentration measuring apparatus according tothe first embodiment, the acoustic wave detection means can also beformed in means for synchronizing the modulation frequency to performthe detection by the synchronous detection. The acoustic wave detectiondescribed in the first embodiment is similar to those of thelater-mentioned second embodiment, third embodiment, fourth embodiment,fifth embodiment, and sixth embodiment.

In the blood constituent concentration measuring apparatus according tothe first embodiment, for example, the photoacoustic signalscorresponding to each of the light beams outputted from the first lightsource 101 and the second light source 105 are detected and convertedinto the electric signals by the ultrasonic detector 113, and theelectric signals are detected by the synchronous detection in which eachof the light beams outputted from the first light source 101 and thesecond light source 105 are synchronized with the intensity-modulatedsignals.

In the phase sensitive amplifier 114, the detection accuracy isincreased in the photoacoustic signals corresponding to the light beamsoutputted from the first light source 101 and the second light source105, which allows the photoacoustic signal to be measured with higheraccuracy.

In the control method of blood constituent concentration measuringapparatus according to the first embodiment, the acoustic wave detectionprocedure can also be formed in a procedure for synchronizing themodulation frequency to perform the detection by the synchronousdetection.

In the control method of blood constituent concentration measuringapparatus according to the first embodiment, for example, thephotoacoustic signals corresponding to each of the two light beamshaving the different wavelengths is synchronized with theintensity-modulated signals of each of the two light beams having thedifferent wavelengths to perform the detection by the synchronousdetection.

The detection accuracy is increased in the photoacoustic signalscorresponding each of to the light beams outputted from the first lightsource 101 and the second light source 105, which allows thephotoacoustic signal to be measured with higher accuracy.

In the blood constituent concentration measuring apparatus according tothe first embodiment, the light generating means and the lightmodulation means can also be formed in means for directly modulatingeach of the two semiconductor laser light sources using therectangular-waveform signals having the same frequency and reversephases. The light generating means described in the first embodiment issimilar to those of the later-mentioned second embodiment, thirdembodiment, fourth embodiment, fifth embodiment, and sixth embodiment.

The two semiconductor laser light sources have apparatus configurationsin which the modulations are directly performed using therectangular-waveform signals having the same frequency and reversephases, which allows the apparatus configuration to be simplified.

In the control method of blood constituent concentration measuringapparatus according to the first embodiment, the light generatingprocedure and the light modulation procedure can be formed in aprocedure in which each of the two semiconductor laser light sources aredirectly modulated using the rectangular-waveform signals having thesame frequency and reverse phases.

The two semiconductor laser light sources are directly modulated usingthe rectangular-waveform signals having the same frequency and reversephases, which allows the apparatus configuration to be simplified.

The detailed technology which is fundamental to the blood constituentconcentration measuring apparatus and control method of bloodconstituent concentration measuring apparatus according to the firstembodiment will be described below.

A configuration of the blood constituent concentration measuringapparatus according to the first embodiment will be described withreference to FIG. 1. As shown in FIG. 1, the blood constituentconcentration measuring apparatus according to the first embodimentincludes the first light source 101, the second light source 105, thedrive circuit 104, the drive circuit 108, the 180°-phase-shift circuit107, the coupler 109, the ultrasonic detector 113, the phase sensitiveamplifier 114, the output terminal 115, and the oscillator 103.

The oscillator 103 is connected to each of the drive circuit 104, the180°-phase-shift circuit 107, and the phase sensitive amplifier 114through signal lines, and the oscillator 103 transmits the signal toeach of the drive circuit 104, the 180°-phase-shift circuit 107, and thephase sensitive amplifier 114.

The drive circuit 104 receives the signal transmitted from theoscillator 103. The drive circuit 104 supplies drive electric power tothe first light source 101, connected to the drive circuit 104 throughthe signal line, to cause the first light source 101 to emit the light.

The 180°-phase-shift circuit 107 receives the signal transmitted fromthe oscillator 103, and the 180°-phase-shift circuit 107 transmits thesignal whose phase is changed by 180°with respect to the received signalto the drive circuit 108 connected to the 180°-phase-shift circuit 107through the signal line.

The drive circuit 108 receives the signal transmitted from the180°-phase-shift circuit 107. The drive circuit 108 supplies driveelectric power to the second light source 105, connected to the drivecircuit 108 through the signal line, to cause the second light source105 to emit the light.

Each of the first light source 101 and the second light source 105outputs the light beams having the different wavelengths, and each ofthe outputted light beams is guided to the coupler 109 by light wavetransmission means.

The light beam outputted from the first, light source 101 and the lightbeam outputted from the second light source 105 are inputted to thecoupler 109, the light beams are multiplexed into one light flux, and apredetermined position of the living body test region 110 is irradiatedwith the light to generate the acoustic wave, i.e., the photoacousticsignal in the living body test region 110.

The ultrasonic detector 113 detects the photoacoustic signal of theliving body test region 110 to convert the photoacoustic signal into theelectric signal, and the ultrasonic detector 113 transmits the electricsignal to the phase sensitive amplifier 114 connected to the ultrasonicdetector 113 through the signal line.

The phase sensitive amplifier 114 receives the synchronous signaltransmitted from the oscillator 103. The synchronous signal is necessaryfor the synchronous detection. The phase sensitive amplifier 114 alsoreceives the electric signal transmitted from the ultrasonic detector113. The electric signal is proportional to the photoacoustic signal.Then, the phase sensitive amplifier 114 performs the synchronousdetection, amplification, and filtering to output the electric signalwhich is proportional to the photoacoustic signal to the output terminal115.

The first light source 101 is synchronized with the oscillationfrequency of the oscillator 103 to output the intensity-modulated light.On the other hand, the second light source 105 is synchronized with theoscillation frequency of the oscillator 103, which is of the signalwhose phase is changed by 180° by the 180°-phase-shift circuit 107, tooutput the intensity-modulated light.

Thus, in the blood constituent concentration measuring apparatusaccording to the first embodiment, the light outputted from the firstlight source 101 and the light outputted from the second light source105 are intensity-modulated using the signals having the same frequency.Therefore, in the blood constituent concentration measuring apparatusaccording to the first embodiment, there is no problem of the unevennessof the frequency characteristics of the measuring system which becomestroublesome when the intensity modulation is performed with the pluralfrequencies in the conventional technique.

On the other hand, the non-linear absorption coefficient dependenceexisting in the measured value of the photoacoustic signal, whichbecomes troublesome in the conventional technique, can be solved byperforming the measurement using the light beams having the pluralwavelengths for giving the equal absorption coefficient in the bloodconstituent concentration measuring apparatus according to the firstembodiment.

That is, in the case where background absorption coefficients α₁ ^((b)),α₂ ^((b)) and molar absorptions α₁ ⁽⁰⁾, α₂ ⁽⁰⁾ of the blood constituentset as the measuring object are already known for light beams having awavelength λ₁ and wavelength λ₂ respectively, the simultaneous equationsincluding measured values s₁ and s₂ of the photoacoustic signal in thewavelengths are expressed by the formula (1). The unknown bloodconstituent concentration M is determined by solving the formula (1). Atthis point C is a variable coefficient which is hardly controlled orcalculated, i.e., C is an unknown multiplier depending on an acousticcoupling state, ultrasonic detector sensitivity, a distance between theirradiation portion and the detection portion (hereinafter defined asr), specific heat, a thermal expansion coefficient, sound velocity, themodulation frequency, and the absorption coefficient.

When the difference is generated in Cs of the first line and second lineof the formula (i), the difference is uniquely an amount concerning theirradiation light, i.e., the difference by the absorption coefficient.At this point, when a combination of the wavelength λ₁ and thewavelength λ₂ is selected such that the parentheses of the lines of theformula (1), i.e., the absorption coefficients are equal to each other,the absorption coefficients are equal to each other, and C in the firstline is equal to C in the second line. However, when the above operationis exactly performed, it is inconvenient because the combination of thewavelength λ₁ and the wavelength λ₂ depends on the unknown bloodconstituent concentration M.

At this point, the background (α₁ ^((b)), i=1 and 2) is remarkablylarger than a term (Mα_(i) ⁽⁰⁾ including the blood constituentconcentration M in an occupying ratio in the absorption coefficient(parenthesis in each line) of the formula (1). In the case, the problemis sufficiently solved by equalizing the absorption coefficient of thebackground α_(i) ^((b)) instead of precisely equalizing the absorptioncoefficient in each line. That is, the two light beams having themutually different wavelength λ₁ and wavelength λ₂ may be selected suchthat the absorption coefficients α₁ ^((b)) and α₂ ^((b)) of thebackground are equal to each other. Thus, when C in the first line isequalized to C in the second line, Cs are deleted as an unknownconstant, and the blood constituent concentration M of the measuringobject is expressed by the following formula (4).

$\begin{matrix}\begin{matrix}{M = \frac{\left( {s_{1} - s_{2}} \right)\alpha_{1}^{(b)}}{{s_{2}\alpha_{1}^{(0)}} - {s_{1}\alpha_{2}^{(0)}}}} \\{\cong {\frac{\alpha_{1}^{(b)}}{\alpha_{1}^{(0)} - \alpha_{2}^{(0)}}\frac{s_{1} - s_{2}}{s_{2}}}}\end{matrix} & \left\lbrack {{Formula}\mspace{14mu} 4} \right\rbrack\end{matrix}$In the deformation of the rear stage of the formula (4), quality ofs₁≅s₂ is used.

Referring to the formula (4), in the denominator, the difference inabsorption coefficient of the blood constituent of the measuring objectemerges in wavelength λ₁ and wavelength λ₂. As the difference isincreased, the difference signal s₁−s₂ of the photoacoustic signal isincreased, and the measurement becomes easy. In order to maximize thedifference, it is good that the wavelength in which the constituentabsorption coefficient α₁ ⁽⁰⁾ of the measuring object becomes themaximum is selected as the wavelength and the wavelength in which α₂⁽⁰⁾=0, i.e., the constituent of the measuring object does not exhibitthe absorption characteristics is selected as the wavelength λ₂. At thispoint, from the condition in the second wavelength λ₂, it is necessarythat α₁ ^((b))=α₂ ^((b)), i.e., the background absorption coefficient isequal to the absorption coefficient of the first wavelength λ₁.

In addition in the formula (4), the photoacoustic signal s₁ emerges onlyin the form of the difference of s₁−s₂ between the photoacoustic signals₁ and the photoacoustic signal s₂. For example, when glucose is set atthe constituent of the measuring object, as described above, there isonly the difference 0.1% or less between the intensity of thephotoacoustic signal s₁ and the intensity of the photoacoustic signals₂.

However, in the denominator of the formula (4), it is sufficient thatthe photoacoustic signal s₂ has the accuracy of about 5%. Accordingly,the accuracy is easily kept in measuring the difference s₁−s₂ betweenthe photoacoustic signal s₁ and the photoacoustic signal s₂ to dividethe measured value by the separately measured photoacoustic signal s₂rather than sequentially separately measuring the photoacoustic signals₁ and the photoacoustic signal s₂. Accordingly, in the bloodconstituent concentration measuring apparatus according to the firstembodiment, when the light beams having the wavelength λ₁ and wavelengthλ₂ are intensity-modulated into the light beams having the reversephases to irradiate the living body, the difference signal s₁−s₂ of thephotoacoustic signals is measured. The difference signal s₁−s₂ of thephotoacoustic signals is generated in the living body while thephotoacoustic signal s₁ and the photoacoustic signal s₂ are mutuallysuperposed.

As described above, in measuring the blood constituent concentration,using the two light beams having the mutually different particularwavelengths, the measurement is performed not by separately measuringthe photoacoustic signals generated in the living body, but by measuringthe difference between the photoacoustic signals, and furthermoremeasuring one of the photoacoustic signals while the other photoacousticsignal is set to zero, and computing the measured values by the formula(4). Therefore, the blood constituent concentration can easily bemeasured.

Then, the acoustic pressure generated by the light irradiation will bedescribed with reference to FIG. 2. FIG. 2 is an explanatory view of abase direct photoacoustic method according to the first embodiment, andFIG. 2 shows an arrangement of an observation point in the directphotoacoustic method along with sound source distribution models. InFIG. 2, light irradiation 201 is perpendicularly incident to the livingbody, which generates a sound source 202 near the surface of the regionirradiated with the light as described above.

For the acoustic wave which is generated from the sound source 202 topropagate through the living body (for the sake of simplicity, it isassumed that acoustic wave is even), acoustic pressure p(r) of theacoustic wave is observed at an observation point 203. The observationpoint 203 is located on the extension line of the irradiation light andthe observation point 203 is separated away from the sound source by adistance r.

In the living body, the background (water) exhibits the strongabsorption for the light having the wavelength 1 μm or longer, which isused in the blood constituent concentration measuring apparatusaccording to the first embodiment, so that the sound source 202 islocalized in the surface of the region irradiated with the light. As aresult, the generated acoustic wave is regarded as a spherical wave.

A wave equation, which describes the acoustic wave propagation shown inFIG. 2, is determined from an equation of fluid dynamics. That is,assuming that a density change, a pressure change, and a flow velocitychange are small, an equation of continuity and a Navier Stokes equationare set as linear equations, and the equation of continuity, the NavierStokes equation, and a state equation which described a relationshipbetween the pressure and the density in the fluid (water) aresimultaneously solved to determine the wave equation. At this point, thestate equation includes a temperature as a parameter, and temperaturechange is captured through the state equation when a heat source Qexists.

When heat transfer is neglected, the micro pressure change p isdescribed by an inhomogeneous Helmholtz equation.

$\begin{matrix}{{\left( {{\frac{1}{c^{2}}\frac{\partial^{2}}{\partial t^{2}}} - \nabla^{2}} \right)p} = {\frac{\beta}{C_{p}}\frac{\partial Q}{\partial t}}} & \left\lbrack {{Formula}\mspace{20mu} 5} \right\rbrack\end{matrix}$Where c is sound velocity, β is a thermal expansion coefficient, andC_(p) is a specific heat capacity at constant pressure.

In the case of the blood constituent concentration measuring apparatusaccording to the first embodiment, the living body is irradiated withthe light, which is intensity-modulated at a constant period T, and anacoustic pressure change, is detected in synchronization with theconstant period T. Therefore, assuming that modulation frequency is setas f=1/T and modulation angular frequency is set as ω=2πf, it isnecessary to pay notice only to the amount having time dependence exp(−iωt) in all the mounts. As a result, time differentiation becomes aproduct with −iω.

Because the heat source Q is caused by non-radiative relaxationsubsequent to the irradiation light absorption, the heat source Q isproportional to the absorption coefficient α and a distribution of theheat source Q is equal to a spatial distribution of irradiation light(including scattered light if exist) in a medium. That is, when thelight intensity is set at I at each point, Q=αI is obtained. Thus, thebasic equation for the steady-state direct photoacoustic method isexpressed by the following formula (6).

$\begin{matrix}{{\left( {\nabla^{2}{+ k^{2}}} \right)p} = {{\mathbb{i}}\frac{\beta}{C_{p}}{\alpha\omega}\;{I.}}} & \left\lbrack {{Formula}\mspace{14mu} 6} \right\rbrack\end{matrix}$At this point, a wave number k=ω/c=2πλ₁ (λ is a wavelength of anacoustic wave) of the acoustic wave is introduced.

In a sufficiently distant site (r) α⁻¹), the solution is expressed bythe following formula (7) under a boundary condition of p (r→∞)→0 of theformula (6).

$\begin{matrix}{{p(r)} = {\frac{1}{4\pi\;{\mathbb{i}}}\frac{\beta}{C_{p}}{\alpha\omega}{\int_{V^{\prime}}^{\;}{\frac{{I\left( \overset{\rightarrow}{r^{\prime}} \right)}{\exp\left\lbrack {{\mathbb{i}}\; k{{\overset{\rightarrow}{r} - \overset{\rightarrow}{r^{\prime}}}}} \right\rbrack}}{{\overset{\rightarrow}{r} - \overset{\rightarrow}{r^{\prime}}}}\ {\mathbb{d}\overset{\rightarrow}{r^{\prime}}}}}}} & \left\lbrack {{Formula}\mspace{14mu} 7} \right\rbrack\end{matrix}$

For some light distributions, the observed acoustic pressure is computedby the formula (7). A model A 204 of the light distribution is assumedto be a hemispherical distribution in which the intensity is attenuatedat a rate of e^(−αr′) with respect to a moving radius r′. The model A204 corresponds to the case where the scattering is significantly largeand the light beams are scattered all the directions once theirradiation light beams are incident.

On the other hand, model B 205 and a model C 206 shown in FIG. 2correspond to the case where the scattering is not generated, and themodel B 205 and the model C 206 correspond to the case where a Gaussiantype beam having a radius w₀ and uniformly circular beam having theradius w₀ are incident. The light intensity distribution of each modelis shown in FIG. 2.

In addition to the already used condition of r>>α⁻¹, when r>>w₀ and N=w₀²/(rλ)<<1 (N is defined with α⁻¹ instead of w₀ for the model A) hold,the computation result by the formula (7) is summarized as follows:

$\begin{matrix}{{p(r)} = {\frac{\beta\; c}{4\pi\; C_{p}}\alpha\;{F\left( {k\;\alpha^{- 1}} \right)}P_{0}\frac{{\mathbb{e}}^{{\mathbb{i}}\;{kr}}}{{\mathbb{i}}\; r}}} & \left\lbrack {{Formula}\mspace{14mu} 8} \right\rbrack\end{matrix}$Where P0 is all power of the irradiation light, and F(ξ) is computed asfollows:

$\begin{matrix}{{F(\xi)} = \left\{ \begin{matrix}{{\arctan(\xi)} - {\left( {{\mathbb{i}}/2} \right){\log\left( {1 + \xi^{2}} \right)}}} & {{for}\mspace{14mu} A} \\{\xi/\left( {1 + {\mathbb{i}\xi}} \right)} & {{{for}\mspace{14mu} B},C}\end{matrix} \right.} & \left\lbrack {{Formula}\mspace{14mu} 9} \right\rbrack\end{matrix}$The information on the sound source distribution is consolidated intothe shape function F(kα⁻¹). FIG. 3 shows a graph of the shape function.

According to the above result, when ξ=kα⁻¹ is small, i.e., when theacoustic wave wavelength is much longer than the absorption length (λ)a−1), the photoacoustic signal does not include any pieces of theinformation on the absorption coefficient. This is because F(ξ)≅ξ inξ<<1 leads to αF(ξ)≅k. Accordingly, when the acoustic wave wavelength ismuch longer than the absorption length, i.e., when the modulationfrequency is excessively low, it is found that the blood constituentconcentration cannot be measured by the photoacoustic method.

Accordingly, in the direct photoacoustic method in which the measurementis performed to the living body, it is necessary that the modulationfrequency is set to i.e., f≅αc/(2π) or more. In the case where theirradiation light wavelength is close to 1.6 μm, it is necessary thatthe modulation frequency f is set to 150 kHz or more. In the case wherethe irradiation light wavelength is close to 2.1 μm, it is necessarythat the modulation frequency f is set to 0.6 MHz or more.

Because there is no difference in the results of the model B 205 andmodel C 206, it is found that the intensity distribution of the lightperpendicular to an optical axis has no influence on the signal.However, the simplification can be permitted only in the case where N=w₀²/(rλ)<<1 holds. N is an amount called Fresnel number, and the Fresnelnumber N indicates a phase change width generated by contribution of theacoustic wave from each point of the sound source according to theexpansion of the sound source in the direction perpendicular to a visualaxis when the sound source is viewed from the observation point. TheFresnel number sufficiently smaller than 1 is equivalent to the factthat the sound source is not enlarged in the direction perpendicular tothe visual axis.

In this case, there is generated an extremely convenient feature thatthe beam diameter w₀ of the irradiation light has no influence on thephotoacoustic signal. The following two reasons can be cited.

First, the influence of the scattering is suppressed in the living body.It is assumed that the model A 204 is the limit state where thescattering is large. However, in the living body, actually the degree ofthe scattering is not so large as compared with the model A 204.Generally, the scattering phenomenon is characterized by a scatteringcoefficient μ_(s) and anisotropy g. The anisotropy g is an average <cosθ> of a cosine of a scattering angle θ, and it is reported that theanisotropy g is approximately 0.9 as a value of the living body,particularly the value of a skin (for example, see Journal of AppliedOptics, vol. 32, 1993, pp 435-447). That is, the scattering in theactual living body mainly includes small angle scattering <θ>≅26°.

A rate at which the light is decreased from the incident light flux bythe scattering during the light propagation in a unit length is given bya reduction scattering coefficient μ′_(s)=μ_(s)(1−g), and the reductionscattering coefficient μ′_(s)=μ_(s)(1−g) of about 1 mm⁻¹ is actuallymeasured for the light wavelength 1 μm or longer (see Non-PatentDocument 3). The reduction scattering coefficient μ′_(s)=μ_(s)(1−g) ofabout 1 mm⁻¹ has the degree similar to the value of the absorptioncoefficient α (0.6 mm⁻¹ for the light wavelength of about 1.6 μm and 2.4mm⁻¹ for the light wavelength of about 2.1 μm) which is of the rate atwhich the light is decreased from the incident light flux by theabsorption during the light propagation in a unit length.

That is, in the living body, the irradiation light receives thescattering only two times during the absorption length α⁻¹, and thescattering angle is small. As a result, the light distribution (sum ofthe incident light flux and the scattering light) in the living body isgradually enlarged in the beam diameter direction as the depth isincreased, and the light distribution is apparently formed in a pinhead.An actual observation example of the above light distribution is alsoreported (see Journal of Applied Optics, vol. 40, 2001, pp 5770-5777).At this point, in a plane of a depth z, it is expected that the totalamount of light distribution is still attenuated according to theexp(−αZ). This is because same scattering is generated at smallscattering angles.

Accordingly, in the case where the photoacoustic signal is independentof the beam diameter of the irradiation light, the beam diameter of thelight distribution at each depth does not become problematic, and onlythe total amount of light distribution at each depth has an influence onthe shape function F(λ) When the light distribution is exp(−αz),resultantly the light distribution is similar to the cases of the modelB 205 and model C 206 in which the scattering is not generated.Therefore, it is expected that the scattering has no influence on theshape function.

In the irradiation with light beams having the wavelength λ₁ and thewavelength λ₂, it is essential to equalize the shape functions in themethod of the first embodiment. Accordingly, it is not desirable thatthe difference in scattering exists in the wavelength λ₁ and thewavelength λ₂. There is no actual measurement report on which thescattering dependence on the wavelength in the skin for the lightwavelength 1.3 μm or longer. However, the constant reduction scatteringcoefficient μ′ is reported for the blood (see Journal of BiomedicalOptics, vol. 4, 1999, p 36-46).

Accordingly, for example, even if the scattering slightly has theinfluence on the shape function, the wavelength dependence is small, andthere is a possibility that the scattering actually has the influence onthe shape function. As described above, when the Fresnel number is setsmall, the influence of the scattering itself on the shape function canbe suppressed. Therefore, the equalization of the shape function isjustified irrespective of the scattering dependence on the wavelength,and it is found that the method of the first embodiment has highreliability.

Second, the modulation frequency can be optimized. In the irradiation ofthe human body with the light, there is an acceptable limit of the lightintensity depending on the irradiated region, the wavelength, theirradiation time, and the like. When the beam diameter w₀ is enlarged inthe range where the Fresnel number N is small, the total power P₀ of theirradiation light can be increased to increase the photoacoustic signalwithout exceeding the limit of the light intensity.

Assuming that the limit of the light intensity is set at I_(max), P₀=πw₀²I_(max) and the Fresnel number N is expressed in the form ofN=f/(πcr)(P₀/I_(max)) by the total power P₀. In consideration of thedistance r which is of an amount (for example, about 10 mm in afingertip and about 40 mm in a wrist) determined by the thickness of theliving body test region 110, it is necessary to decrease the total powerP₀ when k, i.e., the modulation frequency f(∝k) is increased while N iskept constant. However, because magnitude of the shape function|F(kα⁻¹)| is not increased in proportion with k, the detected acousticwave is decreased. Accordingly, it is found that the excessively highmodulation frequency is not desirable.

when an acoustic pressure amplitude P_(a) given by the formula (8) isrewritten using N and I_(max), the flowing formula (10) is obtained.

$\begin{matrix}{{Pa} = {{Psup}\frac{{F\left( {k\;\alpha^{- 1}} \right)}}{k\;\alpha^{- 1}}N}} & \left\lbrack {{Formula}\mspace{14mu} 10} \right\rbrack\end{matrix}$

At this point, an acoustic pressure upper limit P_(sup) is expressed bythe following formula (11).

$\begin{matrix}{{Psup} = {\frac{{\pi\beta}\; c}{2{Cp}}{{Im}{ax}}}} & \left\lbrack {{Formula}\mspace{14mu} 11} \right\rbrack\end{matrix}$In the formula (10), |F(ξ)|/ξ is a function which is monotonouslydecreased for ξ, and the low modulation frequency has an advantage onlyfrom the viewpoint of signal amplitude.

In this case, ξ=kα⁻¹ which maximizes∂P_(a)/∂α=−(P_(sup)N/α)ξd(|F(ξ)|/ξ)/dξ, which is of a rate of change forα of the formula (10), gives the optimum modulation frequency. ξ, whichgives the optimum modulation frequency, is 2.49 in the model A 204, andξ is 2½ in the model B 205 and model C 206. The value of |F(ξ)|/ξ is0.620 in the model A 204 for ξ which gives the optimum modulationfrequency, and the value of |F(ξ)|/ξ is ⅓^(1/2) in the model B 205 andmodel C 206. That is, the optimum modulation frequency exists as ameeting point for contradictory demands of the sensitivity between thesignal intensity and the absorption coefficient α.

As described above, it is thought that the light distribution in theactual living body is close to those of the model B 205 and model C 206.Therefore, the optimum modulation frequency is 2πf=1.41cα and, at thispoint, it is expected that the signal amplitude is 57.7% for the maximumvalue P_(sup)N at f→0.

A principle of the blood constituent concentration measuring apparatusaccording to the first will be described below with reference to FIG. 3.The first light source 101 shown in FIG. 1 is intensity-modulated insynchronization with the oscillator 103, and the light outputted by thefirst light source 101 has a waveform shown in an upper part of FIG. 4as light 211 of a first light source (λ₁).

On the other hand, the second light source 105 shown in FIG. 1 is alsointensity-modulated in synchronization with the oscillator 103. Becausethe 180° phase change is imparted to the signal transmitted from theoscillator 103 by the 180°-phase-shift circuit 107, the light outputtedfrom the second light source 105 is intensity-modulated with the signalhaving the reverse phase with respect to the light outputted from thefirst light source 101, and thereby the light outputted from the secondlight source 105 has a waveform which is shown as the light of secondlight source (λ₂) 212 in the lower part of FIG. 5.

FIG. 3 shows the signal with which the first light source 101 and thesecond light source 105 are intensity-modulated having a period of 1 μs,namely, the modulation frequency f is 1 MHz and a pulse duty factor is50%.

At this point, in the formula (6), it is assumed that a sinusoidalchange is generated in the irradiation light, and FIG. 3 shows that theliving body is irradiated with the rectangular-waveform light. This isnot contradictory because of the following reason.

The formula (5) is linear, and the constituents having the differentfrequency components can independently be dealt with. The non-linearitypossessed by the Navier Stokes equation itself has the influence on theformula (5), when amplitude of the acoustic wave is increased. However,in the photoacoustic signal in the blood constituent concentrationmeasuring apparatus according to the first embodiment, the generatedacoustic wave is weak and the linear formula (5) can be applied.Although the rectangular-waveform includes an odd-number order harmoniccomponent, the amplitude of the sinusoidal component of the basic periodin the odd-number order harmonic component can be replaced by I of theformula (6). In the light source, the intensity modulation is performedmore easily in the rectangular waveform as compared with the sinusoidalwaveform. Additionally, because the rectangular waveform has thesinusoidal component having the basic period of 4/π=1.27 times, therectangular waveform has slightly better efficiency as compared with thesinusoidal waveform having the same amplitude.

The two light beams having different wavelengths respectively outputtedfrom the first light source 101 and second light source 105 aremultiplexed by the coupler 109, and the living body test region 110 isirradiated with the multiplexed light. At this point, it can be thoughtthat each of the two light beams having the different wavelengthsgenerates the acoustic pressure independently expressed by the formula(8).

From the linearity of the formula (5), it is already clear that theacoustic waves are linearly superposed. The two light beams having thedifferent wavelengths are not so strong to an extent in which theabsorption is saturated, so that the heat generations Q by the two lightbeams having the different wavelengths are also linearly superposed.Even if the absorption is saturated, the linear superposition of theheat generation still holds when the absorption has uneven spread and,at the same time, when the interval between the two light beams havingthe different wavelengths is broader than an even width. Theseconditions are well satisfied for the water in which the absorption iscommonly generated for the two light beams having the differentwavelengths.

As described above, the photoacoustic signals having the acousticpressures independently expressed by the formula (8) are generated bythe two light beams having the different wavelengths, and the superposedacoustic pressure is detected by the ultrasonic detector 113.Accordingly, the superposed acoustic pressure is expressed by thefollowing formula.

$\begin{matrix}\begin{matrix}{{p(r)} = {s_{1} - s_{2}}} \\{= {\frac{\beta\; c}{4\pi\;{Cp}}\left\{ {{\alpha_{1}{F\left( {k\;\alpha_{1}^{- 1}} \right)}} - {\alpha_{2}{F\left( {k\;\alpha_{2}^{- 1}} \right)}}} \right\} P_{0}\frac{{\mathbb{e}}^{{\mathbb{i}}\;{kr}}}{{\mathbb{i}}\; r}}}\end{matrix} & \left\lbrack {{Formula}\mspace{14mu} 12} \right\rbrack\end{matrix}$

At this point, the reason why α_(i)F(kα_(i) ⁻¹) (i=1 and 2) issuperposed in the shape of the difference is that the incident lightbeams of the two light beams having the different wavelengths areintensity-modulated in the reverse phases. The solid line of FIG. 6shows the waveform of the basic-period sinusoidal component in theelectric signal obtained by detecting and converting the acousticpressure by the ultrasonic detector 113. The amplitude (rms value) ofthe signal shown by the solid line in FIG. 6 is measured by the phasesensitive amplifier 114 synchronized with the oscillator 103, and theamplitude is outputted in the form of the signal shown by Vd in FIG. 6to the output terminal 115.

From the formula (12) and the formula (1), the unknown constant C isexpressed by the following formula.

$\begin{matrix}{C = {\frac{\beta\; c}{4\pi\;{Cp}}{F\left( {k\;\alpha^{- 1}} \right)}P_{0}\frac{1}{r}}} & \left\lbrack {{Formula}\mspace{14mu} 13} \right\rbrack\end{matrix}$Then, a principle of computing the blood constituent concentration setas the measuring object using the formula (4) will be described. Becausethe difference signal s₁−s₂ of the photoacoustic signals correspondingto the light beams outputted from the first light source 101 and thesecond light source 105 is already obtained, the blood constituentconcentration M of the measuring object can be computed from the formula(4) when the photoacoustic signal s₂ is measured.

Therefore, the photoacoustic signal is measured while the living body isirradiated only with the light of second light source (λ₂) 212 shown inFIG. 5. That is, as shown in FIG. 5, the output of the first lightsource 101 is caused to become zero while the waveform of the lightoutputted from the second light source 105 is maintained. This can berealized by blocking the light outputted from the first light source 101shown in FIG. 1 with a mechanical shutter or by decreasing the output ofthe drive circuit 104 below an oscillation threshold of the first lightsource 101.

When the value of the photoacoustic signal measured in the above stateis detected and converted into the electric signal by the ultrasonicdetector 113, the waveform shown by the broken line in FIG. 6 isobtained as the basic-period sinusoidal component. Similarly, to theabove method, an rms amplitude of the waveform shown by the broken linein FIG. 6 is measured by the phase sensitive amplifier 114, and the rmsamplitude is outputted in the form of the signal shown by Vr in FIG. 6to the output terminal 115.

The photoacoustic signal S₂ has the reverse phase with respect to thedifference signal s₁−s₂ between the photoacoustic signals. Thephotoacoustic signal S₂ has several orders of magnitude more thedifference signal s₁−s₂ between the photoacoustic signals. For example,in the case of the blood sugar level measurement of the normal subject,the photoacoustic signal S₂ is 1000 times or more the difference signals₁−s₂ between the photoacoustic signals. Accordingly, the sensitivityand a time constant of the phase sensitive amplifier 114 are switchedduring the interval between the measurements of the photoacoustic signalS₂ and the difference signal s₁−s₂ of the photoacoustic signals.

When the two measured values V_(d) and V_(r) are obtained by themeasurements, s₁−s₂ and s₂ in the formula (4) are replaced by the twomeasured values V_(d) and V_(r) to compute the blood constituentconcentration M set as the measuring object.

The specific absorbance α₁ ⁽⁰⁾/α₁ ^((b)) (α₂ ⁽⁰⁾/α₁ ^((b)) is furtherrequired when α₂ ⁽⁰⁾ is not zero) is further required for the conversionof a ratio V_(d)/V_(r) of the measured values to the blood constituentconcentration M.

FIG. 7 shows the specific absorbance value and a method of selecting thewavelength λ₁ and wavelength λ₂ to be measured. As described above, thewavelength λ₁ and wavelength λ₂ have the same background absorptioncoefficient.

FIG. 7 shows a method of selecting the wavelengths corresponded to thefirst light source 101 and the second light source 105 in the bloodconstituent concentration measuring apparatus according the firstembodiment when the blood sugar level is measured.

FIG. 7 shows absorbances (OD) of water and glucose aqueous solution(concentration 1.0M) in the light wavelength range of 1.2 μm to 2.5 μm.The absorbance OD has a relationship of β=OD1n10 with the absorptioncoefficient α. A scale of the absorption coefficient α is shown in avertical axis on the right side of FIG. 7.

In FIG. 7, although it is observed that the absorption by the glucosemolecule exists slightly near 1.6 μm and 2.1 μm, the absorption by theglucose molecule is much smaller than that by the water.

The upper part of FIG. 8 shows the difference in absorbance betweenwater and glucose, and the lower part of FIG. 8 shows the specificabsorbance in which the absorbance is divided by the water absorbance.

From the specific absorbance shown in FIG. 8, it is observed that theclear maximum of the absorbance by the glucose molecule is located at1608 nm and 2126 nm. For example, for the absorption wavelength by theglucose molecule, the wavelength of the first light source 101 is set at1608 nm (specific absorbance is 0.114 M⁻¹). The wavelength λ₁ is shownby the vertical solid line with (o) in FIG. 8.

The absorption coefficient λ₁ ^((b)) of the background (water) at thewavelength 1608 nm is 0.608 mm⁻¹ from FIG. 7. The wavelength λ₂ in whichα₂ ^((b))=α₁ ^((b)) is the wavelength of 1381 nm or the wavelength of1743 nm from the water absorption spectrum of FIG. 7. The value of α₂⁽⁰⁾ is checked with the specific absorbance spectrum of FIG. 8 for eachof the candidates of the wavelength λ₂ of the second light source 105.As a result, while the specific absorbance becomes zero at thewavelength of 1381 nm, the wavelength of 1743 nm is located in theabsorption band of the glucose molecule, and the specific absorbance is0.0601 M⁻¹ at the wavelength of 1743 nm. Because the measurement iseasily performed when the absorbance difference α₁ ⁽⁰⁾−α₂ ⁽⁰⁾ is largeras much as possible, in the case of above, the wavelength of 1381 nm isselected as the wavelength λ₂ of the second light source 105.

In the case where the wavelength of 2126 nm is set at the wavelength λ₁of the first light source 101 (specific absorbance is 0.0890 M⁻¹) in thelong wavelength side, becomes of the same way as described above thewavelengths of 1837 nm and 2294 nm exist as the wavelength in which thewater molecule exhibits the absorption coefficient equal to theabsorption coefficient α₁ ^((b))=2.361 mm⁻¹ at the wavelength of 2126nm. Both the wavelengths of 1837 nm and 2294 nm are located outside theglucose absorption (shown by the vertical dotted line in FIG. 8), sothat either 1837 nm or 2294 nm may be selected as the wavelength λ₂ ofthe second light source 105.

EXAMPLES

Then, specific examples in the first embodiment will be described below.

First Example-1

In the blood constituent concentration measuring apparatus according tothe first embodiment shown in FIG. 1, it is effective that a laser lightsource is used as the first light source 101 and the second light source105. In selecting the laser light source, it is necessary to estimatethe necessary output laser power level.

In irradiating the human body with the light, there is the acceptablelimit of the light intensity. Generally one-tenths of the intensity inwhich affection is generated in 50% individual is defined as the maximumtolerance in JIS C6802. According to JIS C6802, the maximum tolerance is1 mW per 1 mm² in the continuous irradiation of non-visible infraredlight (wavelength 0.8 μm or longer) for the skin.

In a first example, the blood constituent of the measuring object is setat blood sugar, the irradiation light wavelength is set at 1.6 μm, andthe modulation frequency f is set at 150 kHz or more because of theabove-described principle. The wavelength λ=c/f becomes 10 mm or less inthe photoacoustic signal generated in the living body test region 110.When the fingertip is set as the living body test region 110, thedistance r between the irradiation region irradiated with the light andthe detection portion in which the ultrasonic detector 113 comes intocontact with the living body test region 110 becomes 10 mm, the beamdiameter w_(o) having the Fresnel number of N=W₀ ²/(rλ) is computed inW₀ ²≦10 mm². An irradiation light beam area is computed by multiplyingπ. When the maximum tolerance is integrated to compute the maximumirradiation light power, the maximum tolerance becomes 31 mW.

When the irradiation light is set at the 2.1 μm band, the maximum powerbecomes 8 mW from the similar computation, and this optical output cansufficiently be supplied by the semiconductor laser.

The compact semiconductor laser has a long life, and the semiconductorlaser has an advantage that the intensity modulation is easily performedby modulating injection current. Therefore, in the first example, thesemiconductor laser is used as the first light source 101 and the secondlight source 105.

FIG. 9 shows a configuration example of the blood constituentconcentration measuring apparatus according to the first example. Theconfiguration of the first example shown in FIG. 9 of the bloodconstituent concentration measuring apparatus according to the firstembodiment is the forward propagation type which detects the acousticwave propagating in the irradiation light direction, and the firstexample has the configuration similar to the basic configuration of theblood constituent concentration measuring apparatus shown in FIG. 1. Thefirst light source 101, the second light source 105, the drive circuit104, the drive circuit 108, the 180°-phase-shift circuit 107, thecoupler 109, an ultrasonic detector 113, the phase sensitive amplifier114, the output terminal 115, and the oscillator 103 which are shown inFIG. 1 correspond to a first semiconductor light source 501 and a lens502, a second semiconductor light source 505 and a lens 506, a drivecurrent source 504, a drive current source 508, a 180°-phase-shiftcircuit 507, a coupler 509, an ultrasonic detector 513 and an acousticcoupler 512, a phase sensitive amplifier 514, an output terminal 515,and an oscillator 503 which are shown in FIG. 9 respectively. All thecomponents shown in FIG. 9 have the similar functions as those shown inFIG. 1.

However, the light beams outputted from the first semiconductor lightsource 501 and the second semiconductor light source 505 shown in FIG. 9are caused to converge into parallel light fluxes by the lens 502 andlens 506 respectively, the parallel light fluxes are multiplexed by thecoupler 509 into one light flux, and the living body test region 510 isirradiated with the light. The acoustic coupler 512 shown in FIG. 9 isplaced between the ultrasonic detector 513 and the living body testregion 510 to have a function of enhancing photoacoustic signaltransmission efficiency between the ultrasonic detector 513 and theliving body test region 510.

FIG. 9 also shows a calibration test sample 511. The function of thecalibration test sample 511 will be described later.

The first semiconductor light source 501 is intensity-modulated by thedrive current source 504 in synchronization with the oscillator 503, theoutput light is collected into the parallel light flux by lens 502, andthe parallel light flux is inputted to the coupler 509. The secondsemiconductor light source 505 is intensity-modulated by the drivecurrent source 508 in synchronization with the oscillator 503, theoutput light is collected into the parallel light flux by lens 506, andthe parallel light flux is inputted to the coupler 509. At this point,because the output of the oscillator 503 is transmitted to the drivecurrent source 508 through the 180°-phase-shift circuit 507, the lightoutputted from the second semiconductor light source 505 isintensity-modulated by the signal having the reverse phase with respectto the light outputted from the first semiconductor light source 501.

The light beams outputted from each of the first semiconductor lightsource 501 and the second semiconductor light source 505 are inputted tothe coupler 509, and the light beams are multiplexed into one lightflux, and the living body test region 510 is irradiated with the onelight flux.

The light with which the living body test region 510 is irradiatedgenerates the photoacoustic signal in the living body test region 510,the generated photoacoustic signal is detected by the ultrasonicdetector 513 through the acoustic coupler 512, and the photoacousticsignal is converted into the electric signal proportional to theacoustic pressure of the photoacoustic signal.

The synchronous detection, the amplification, and the filtering areperformed to the signal which is detected by the ultrasonic detector 513and converted into the electric signal proportional to the acousticpressure of the photoacoustic signal, and the signal is outputted to theoutput terminal 515 by the phase sensitive amplifier 514 synchronizedwith the oscillator 503.

As described above, the wavelength of the first semiconductor lightsource 501 is set at 1608 nm, and the wavelength of the secondsemiconductor light source 505 is set at 1381 nm. The oscillationfrequency of the oscillator 503, i.e., the modulation frequency f is setat 207 kHz such that ξ=kα₁ ^((b))=2^(1/2) is obtained.

The optical output of the first semiconductor light source 501 is set at5.0 mW, and the optical output of the second semiconductor light source505 is also set at 5.0 mW.

The light beam diameter with which the living body test region 510 isirradiated is set as w₀=2.7 mm such that the Fresnel number N becomes0.1 while the distance r between the irradiation portion and thedetection portion is set at 10 mm.

In this state of things, the irradiation intensity to the skin of theliving body test region 510 is 0.44 mW/mm² in the light in which thelight beams outputted from the first semiconductor light source 501 andsecond semiconductor light source 505 are multiplexed, and theirradiation intensity is in a safe level which is lower than a half ofthe maximum tolerance. However, the irradiation intensity is in adangerous level for eyes. Therefore, it is necessary that lightshielding hoods (not shown in FIG. 9) is placed in the coupler 509 andthe living body test region 510 such that the light reflected orscattered from the acoustic coupler 512 is not directly incident to theeyes during the measurement, or during in which the living body testregion 510 is not placed.

The ultrasonic detector 513 is a frequency flat type electrostrictivedevice (PZT) into which an FET (field effect transistor) amplifier isincorporated, and the acoustic coupler 512 is an acoustic matching gel.

In the above configuration, first the optical output of the firstsemiconductor light source 501 is set to zero, and the living body testregion 510 is irradiated only with the light outputted from the secondsemiconductor light source 505 as shown in FIG. 9. Then, in the outputterminal 515 of the phase sensitive amplifier 514 whose time constant isset at 0.1 second, the voltage of Vr=20 μV is obtained as the electricsignal corresponding to the photoacoustic signal s₂.

At this point, it is necessary to search the optimum phase difference ineach measurement, because the phase difference θ between the synchronoussignal transmitted from the oscillator 503 in the phase sensitiveamplifier 514 and the signal in which the photoacoustic signal isdetected and converted into the electric signal by the ultrasonicdetector 513 is changed by the modulation frequency f and the distance rbetween the irradiation portion where the living body test region 510 isirradiated with the light and the contact portion which comes intocontact with the acoustic coupler 512. It is effective that the searchof the phase difference is performed by measuring the photoacousticsignal s₂ having the large signal amplitude.

In the case of the two-phase type phase sensitive amplifier, because thetype phase sensitive amplifier has ability to always automaticallydetermine the phase difference θ, it is not necessary to manuallyperform the search of the phase difference. That is, the phase andamplitude are determined by measuring the photoacoustic signal s₂ in anR−θ mode in which unknown phase and amplitude can be measured, and usingthe measured value of the phase the difference signal s₁−s₂ of thephotoacoustic signals is measured in an X measuring mode in which theamplitude can be measured while noise suppression ratio is improved by 3dB when the phase is already known.

When the first semiconductor light source 501 emits the light, V_(d)=7.7nV (the direct measured value becomes −7.7 nV because the phase isreversed) is obtained at the output terminal 515 in the form of theelectric signal corresponding to the difference signal s₁−s₂ of thephotoacoustic signals. Then, the optical output of the firstsemiconductor light source 501 is set to zero again, and thephotoacoustic signal s₂ is measured while the sensitivity and timeconstant of the phase sensitive amplifier 514 are returned to theoriginal state, and the voltage of Vr=22 μV is obtained. The value of Vrbecomes 21 μV from the average of the two times of yr.

As described above, it is desirable that the signal corresponding to thephotoacoustic signal s₂, i.e., Vr is measured twice before and aftermeasuring the difference signal s₁−s₂ of the photoacoustic signals.

The drift of the unknown multiplier C can be corrected during measuringthe difference signal s₁−s₂ by the above procedure. The drift of theunknown multiplier C is derived from the change in the distance r causedby the change in pressing force of the fingertip of the subject and fromthe local temperature change caused by the light irradiation.

The glucose concentration M of 3.2 mM (58 mg/dl) is determined from themeasured values, the specific absorbance value 0.114 M⁻¹ at thewavelength of 1608 nm, and the formula (4).

The acoustic pressure upper limit P_(sup) of 0.17 Pa is obtained forI_(max)=1 mW/mm² using the values for the water, i.e., C_(p)=1(cal/g·deg)=4.18×10³ (J/kg·K), β=300 ppm/deg, and c=1.51×10³ (m/s). Whenthe acoustic pressure upper limit P_(sup) is multiplied by the Fresnelnumber N=0.1, the attenuation of ⅓^(1/2) associated with ξ=2^(1/2), andan actual irradiation power ratio of 0.22, the expected amplitude of theacoustic pressure is 2.1 mPa.

On the contrary, because nominal sensitivity of the ultrasonic detector513 is 66 mV/Pa, it is calculated the output voltage of the outputterminal 515 is 140 μV. However, the actually measured value of thephotoacoustic signal s₂ is one-sevenths of 140 μV. This is attributed tothe incompleteness of the acoustic coupler 512.

First Example-2

In a first example-2, for the purpose of the improvement of the acousticcoupling state, an acryl plate having the thickness of 6.6 mm is formedin the same diameter of 10 mmφ as that of the ultrasonic detector 513 inorder to cause the acoustic coupler 512 to be a resonance type. One ofthe surfaces of the acoustic coupler 512 is attached to the ultrasonicdetector 513 through vacuum grease, and the other surface is in contactwith the living body test region 510 through the acoustic matching gel.

In the above configuration, as a result of the two-time measurement inthe same procedure, the measured values of the photoacoustic signal s₂are 150 nV and 153 μV, and the measured value of the difference signals₁−s₂ between the photoacoustic signals is 59 nV. In the abovemeasurement, the time constant of the phase sensitive amplifier 514 isthree seconds. The glucose concentration M of 3.4 mM (61 mg/dl) isdetermined from the measured values.

First Example-3

In the first Example-2, the resonant frequency does not completelycoincide with the modulation frequency f in the acoustic coupler 512.Therefore, in a first Example-3, during measuring the forestagephotoacoustic signal s₂, the frequency of the oscillator 503 is swept ina range of several percent to operate the two-phase type phase sensitiveamplifier 514 in the R−θ mode, and the modulation frequency f is setsuch that the output of the signal output terminal 515 becomes themaximum. Therefore, in the acoustic coupler 512, the resonant frequencyis caused to completely coincide with the modulation frequency f.

Through the same procedures as the first Example-2 except for the aboveprocedure, 600 μV and 604 μV are obtained by the two-time measurements.The measured value of the difference signal s₁−s₂ between thephotoacoustic signals is 0.25 nV. In this case, the time constant of thephase sensitive amplifier 514 is one second. The glucose concentration Mof 3.6 mM (65 mg/dl) is determined from the measured values.

The frequency flat type electrostrictive device (PZT) is used as theultrasonic detector 513 in the first Example-1, first Example-2, andfirst Example-3. However, even in the normal type electrostrictivedevice (PET), by searching the modulation frequency f in which theamplitude of the signal obtained at the output terminal 515 is maximum,the measurement can be performed with the increased sensitivity byutilizing resonance characteristics. Therefore, the normal typeelectrostrictive device (PET) is suitable for the miniaturization andcost reduction.

First Example-4

A first Example-4 is a case where the calibration test sample 511 isintroduced as the means for adjusting the light powers outputted fromthe first semiconductor light source 501 and the second semiconductorlight source 505 such that the light power are equalized.

In the configuration of the calibration test sample 511, water is sealedin a glass container, or the water in which the scatterers, such aslatex powders, are dispersed is sealed in the glass container. Thescatterers such as latex powders simulate the scattering in the livingbody.

In order to secure the evenness of the transmittances for the wavelengthλ₁ and wavelength λ₂ in the glass of the surface of the calibration testsample 511, which is irradiated with the light (upper surface in FIG.9), it is effective that a pipe shaped margin having a diameter throughwhich the irradiation beam passes is provided in the upper surface ofthe calibration test sample 511 to prevent the direct contact with thesurface, or it is effective that the calibration test sample 511 iscleaned with a predetermined product through a predetermined procedurebefore the use of the calibration test sample 511.

The calibration procedure in which the calibration test sample 511 isattached instead of the living body test region 510 is performed asfollows.

First the optical output of the first semiconductor light source 501 isset to zero, and the calibration test sample 511 is irradiated only withthe light outputted from the second semiconductor light source 505 asshown in FIG. 9. The two-phase type phase sensitive amplifier 514 isoperated in the R−θ mode, and the phase θ at that time is determined andfixed. In the resonance type ultrasonic wave detection, at this stage,similarly the optimum modulation frequency f is searched in order tocause the resonant frequency and modulation frequency of the acousticcoupler 512 to coincide with each other.

First the decrease in signal outputted to the output terminal 515 of thephase sensitive amplifier 514 is observed while the light outputted tothe first semiconductor light source 501 is increased, and thesensitivity and time constant of the phase sensitive amplifier 514 arechanged in accordance with the decrease in signal outputted to theoutput terminal 515. Then, the optical output of the first semiconductorlight source 501 is fixed at the time when the output obtained at theoutput terminal 515 becomes zero.

Through the above procedure, the calibration can be performed with thecalibration test sample 511 into the state, in which the relativeintensity of the light outputted from the first semiconductor lightsource 501 and the relative intensity of the light outputted from thesecond semiconductor light source 505 are equal to each other and thelight beams outputted from the first semiconductor light source 501 andsecond semiconductor light source 505 are intensity-modulated by thesignals having the reverse phases.

A method of turning on a power supply of the blood constituent measuringapparatus according to the first example-4 while the calibration testsample 511 is attached instead of the living body test region 510 can bedefined to perform the above sequences as POST (Power On Self Test) in apower-on operation.

Second Example-1

A second example-1 is a rearward propagation type which detects theacoustic wave propagating in the opposite direction to the irradiationlight. As shown in FIG. 10, the configuration of the second example hasthe configuration in which, in the configuration of the first example ofthe blood constituent concentration measuring apparatus shown in FIG. 9,the acoustic coupler 512 is placed between the coupler 509 and theliving body test region 510, one of the surfaces of the acoustic coupler512 is in contact with the living body test region 510, the lightmultiplexed by the coupler 509 is incident to the other surface of theacoustic coupler 512, the incident light passes through the acousticcoupler 512, and the living body test region 510 is irradiated with thelight. The ultrasonic detector 513 is placed on the side where themultiplexed light is incident to the acoustic coupler 512.

The operation of the blood constituent concentration measuring apparatusaccording to the second example-1 differs from that of the first examplein that, as shown in FIG. 10, the light outputted from the coupler 509passes through the acoustic coupler 512, the living body test region 510is irradiated with the light, the photoacoustic signal generated in theliving body test region 510 propagates through the acoustic coupler 512again, and the photoacoustic signal is detected by the ultrasonicdetector 513.

In the above configuration, because the irradiation light passes throughthe acoustic coupler 512, it is desirable that the acoustic coupler 512has the small light absorption and the acoustic impedance close to theliving body (water).

In the second example-1, the acoustic coupler 512 is made of quartzglass having the small light absorption. The quartz glass has theacoustic impedance eight times the water, only about one-fifths of thegenerated acoustic pressure becomes the propagation wave in the quartzglass, and the acoustic pressure is observed by the ultrasonic detector513. Accordingly, because the quartz glass brings a disadvantage fromthe viewpoint of sensitivity, it is necessary that the acoustic coupler512 itself has the resonance characteristics to increase thesensitivity. That is, the thickness (corresponding to the propagationlength of the light flux in the glass in the drawing) of the quartzglass is set at 14 mm which becomes a substantially half of thewavelength (λ=27.85 mm) of the acoustic wave for the modulationfrequency f of 200 kHz.

The acoustic wave in the quartz glass is regarded as the spherical wavein the far site from the living body test region 510, so that theultrasonic detector 513 is placed at an angle of 150° with respect tothe incident light flux (when the ultrasonic detector having a holethrough which the incident light flux passes is used, the ultrasonicdetector can be placed in the completely rearward direction of 180°).

In the configuration of the second example-1, the distance r between theirradiation portion where the living body test region 510 is irradiatedwith the light and the detection unit where the ultrasonic detector 513detects the photoacoustic signal in the acoustic coupler 512 is fixed toa constant value (in this case, r=14 mm) which is determined by a sizeof the acoustic coupler 512.

The first semiconductor light source 501, the second semiconductor lightsource 505, and the ultrasonic detector 513 are similar to those of thefirst example. For the purpose of safety, a test body sensing switch(neglected in FIG. 10) is arranged such that light irradiation is notperformed when no object is placed on the acoustic coupler 512.

Similarly to the first example, during measuring the forestagephotoacoustic signal s₂, the frequency of the oscillator 503 is swept tosearch the modulation frequency f which coincides with the resonantfrequency of the acoustic coupler 512. Through the same procedure as thefirst example, 200 μV and 206 μV are obtained as the photoacousticsignal s₂ by the two-time measurements. The measured value of thedifference signal s₁−s₂ between the photoacoustic signals is 79 nV whenthe time constant of the phase sensitive amplifier 514 is set at onesecond. The glucose concentration M of 3.4 mM (61 mg/dl) is determinedfrom the measured values.

Second Example-2

In the second example-2, the acoustic coupler 512 is made of low-densitypolyethylene. The low-density polyethylene is excellent for the acousticwave coupling (pressure loss is lower than 9%) because the acousticimpedance of the low-density polyethylene differs from that of the wateronly by 18%. However, the low-density polyethylene slightly absorbs thelight and the low-density polyethylene is excessively soft. However, thelow-density polyethylene has the advantage in that, due to the softness,the low-density polyethylene comes into close contact with the livingbody not to require a supply material such as the acoustic matching gel.High-density polyethylene having the rigidity is not suitable becausethe high-density polyethylene is not transparent for the light.

In the second example-2, the thickness of the acoustic coupler 512 isset at 10 mm which is substantially equal to the acoustic wavewavelength for the modulation frequency f of 200 kHz, and the distance rbetween the irradiation portion and the detection portion is also set atthe fixed value of 10 mm.

Similarly to the second example-1, 300 μV and 289 μV are obtained as thephotoacoustic signal s₂ by the two-time measurements. The measured valueof the difference signal s₁−s₂ between the photoacoustic signals is 117nV when the time constant of the phase sensitive amplifier 514 is set atone second. The glucose concentration M of 3.5 mM (63 mg/dl) isdetermined from the measured values.

The reason why the measured signal is not increased while thelow-density polyethylene has the low-pressure loss is that the acousticcoupler 512 is deformed by the pressing force of the living body testregion 510 and thereby the size becomes unstable to insufficientlyincrease the sensitivity improvement by the resonance.

Second Example-3

The second example-3 is the case where the calibration means with thecalibration test sample 511 is introduced to the second example-2. Inthis case, in the calibration test sample 511, the container in whichthe water or the water containing the scatterers is sealed is made ofthe same material as the acoustic coupler 512.

The surface irradiated with the light is the surface of which thecalibration test sample 511 is in contact with the acoustic coupler 512shown in FIG. 10. In order to secure cleanness for a long term, thecalibration test sample 511 is cleaned with the predetermined productthrough the predetermined procedure before the use of the calibrationtest sample 511.

The calibration procedure, which is performed by attaching thecalibration test sample 511, instead of the living body test region 510and the like are similar to the first example-4.

Third Example

Examples for the glucose concentration in the blood, i.e., the bloodsugar level are shown in the first example and the second example.However, in addition to the glucose, the blood contains many componentssuch as cholesterol, lipid, protein, and an inorganic component. Theblood constituent concentration measuring apparatus and control methodof blood constituent concentration measuring apparatus according to thefirst embodiment are applied to cholesterol in a third example. Theblood constituent concentration measuring apparatus and control methodof blood constituent concentration measuring apparatus in the thirdexample can also be applied in examples in the later-mentioned secondembodiment, third embodiment, fourth embodiment, fifth embodiment, andsixth embodiment.

FIG. 11 shows the absorbance of water in a frequency range of 1200 nm to2500 nm. FIG. 12 shows the absorbance of cholesterol in a frequencyrange of 1600 nm to 2600 nm. Referring to the spectrum shown in FIG. 12,it is observed that the clear maximum of the absorption by thecholesterol molecule exists in 2310 nm.

The absorption coefficient α₁ ^((b)) of the background (water) at thewavelength of 2310 nm is 1.19 mm⁻¹ from FIG. 11. The wavelength λ₂ inwhich α₂ ^((b))=α₂ ^((b)) is obtained is the wavelength of 2120 nm orthe wavelength of 1880 nm from the water absorption spectrum of FIG. 11.The value of α₂ ^((b)) is confirmed for each of the candidates of thewavelength λ₂ of the second light source 105 by the absorption spectrumof FIG. 12. As a result, in the cholesterol molecule, it is found thatthe absorption is large at the wavelength of 1880 nm as compared withthe absorption in the wavelength of 2120 nm. Because the measurement iseasily performed when the absorbance difference α₁ ⁽⁰⁾−α₂ ⁽⁰⁾ is largeas much as possible, in this case, 2120 nm is selected as the wavelengthof the second light source. Accordingly, the measurement is performedwhile the wavelength of the first light source is set at 2310 nm and thewavelength of the second light source is set at 2120 nm.

FIG. 13 shows a configuration of the blood constituent concentrationmeasuring apparatus according the third example. The configuration ofthe third example of the blood constituent concentration measuringapparatus shown in FIG. 13 is the forward propagation type which detectsthe photoacoustic signal propagating in the irradiation light direction.The third example has the basic configuration similar to that of theblood constituent concentration measuring apparatus shown in FIG. 1.

That is, a first semiconductor light source 801 and a lens 802, a secondsemiconductor light source 805 and a lens 806, a drive current source804, a drive current source 808, a 180°-phase-shift circuit 807, acoupler 809, an ultrasonic detector 813 and an acoustic coupler 812, aphase sensitive amplifier 814, an output terminal 815, and an oscillator803 which are shown in FIG. 13 have the same functions as those of thefirst light source 101, the second light source 105, the drive circuit104, the drive circuit 108, the 180°-phase-shift circuit 107, thecoupler 109, the ultrasonic detector 113, the phase sensitive amplifier114, the output terminal 115, and the oscillator 103 which are shown inFIG. 1 respectively.

The first semiconductor light source 801 is intensity-modulated by thedrive current source 804 in synchronization with the oscillator 803, theoutput light is collected into the parallel light flux by lens 802, andthe parallel light flux is inputted to the coupler 809. The secondsemiconductor light source 805 is also intensity-modulated by the drivecurrent source 808 in synchronization with the oscillator 803, theoutput light is collected into the parallel light flux by lens 806, andthe parallel light flux is inputted to the coupler 809.

At this point, because the output of the oscillator 803 is transmittedto the drive current source 808 through the 180°-phase-shift circuit807, the light outputted from the second semiconductor light source 805is intensity-modulated by the signal having the reverse phase withrespect to the light outputted from the first semiconductor light source801.

The light beams outputted from the first semiconductor light source 801and the second semiconductor light source 805 are inputted to thecoupler 809, and the light beams are multiplexed into one light flux,and the living body test region 810 which is of the test subject isirradiated with the one light flux.

The light with which the living body test region 810 is irradiatedgenerates the photoacoustic signal in the living body test region 810,the generated photoacoustic signal is detected by the ultrasonicdetector 813 through the acoustic coupler 812, and the ultrasonicdetector 813 converts the photoacoustic signal into the electric signalproportional to the acoustic pressure of the photoacoustic signal.

The phase sensitive amplifier 814 performs synchronized the oscillatorthe synchronous detection, the amplification, and the filtering to thesignal converted into the electric signal, and the phase sensitiveamplifier 814 outputs the signal to the output terminal 815.

The wavelength of the first semiconductor light source 801 is set at2310 nm, and the wavelength of the second semiconductor light source 805is set at 2120 nm. The oscillation frequency of the oscillator 803,i.e., the modulation frequency f is set at 207 kHz such that ξ=kα₁^((b))=2^(1/2) is obtained.

The optical output of the first semiconductor light source 801 is set at5 mW, and the optical output of the second semiconductor light source805 is also set at 5 mW.

The light beam diameter with which the living body test region 810 isirradiated is set as w₀=2.7 mm such that the Fresnel number N becomes0.1 while the distance r between the irradiation portion and thedetection portion in the living body test region 810 is set at 10 mm.

In this state of things, the irradiation intensity to the skin of theliving body test region 810 is 0.44 mW/mm² in the light in which thelight beams outputted from the first semiconductor light source 801 andthe second semiconductor light source 805 are multiplexed, and theirradiation intensity is in the safe level which is lower than a half ofthe maximum tolerance. However, in consideration of the leakage to theoutside, it is preferable that light shielding hoods (not shown) isplaced in the coupler 809 and the living body test region 810.

The ultrasonic detector 813 is the frequency flat type electrostrictivedevice (PZT) into which the field effect transistor (FET) amplifier isincorporated. An acoustic matching gel is used as the acoustic coupler812.

In the above configuration of FIG. 13, the optical output of the firstsemiconductor light source 801 is set to zero, and the living body testregion 810 is irradiated only with the light outputted from the secondsemiconductor light source 805. Then, in the output terminal 815 of thephase sensitive amplifier 814 whose time constant is set at 0.1 second,the voltage of Vr=40 μV is obtained as the electric signal correspondingto the photoacoustic signal s₂.

It is necessary to search the optimum phase difference in eachmeasurement, because the phase difference θ between the synchronoussignal transmitted from the oscillator 803 in the phase sensitiveamplifier 814 and the signal in which the photoacoustic signal isdetected and converted into the electric signal by the ultrasonicdetector 813 is changed by the modulation frequency f and the distance rbetween the irradiation portion where the living body test region 810 isirradiated with the light and the contact portion which comes intocontact with the acoustic coupler 812. It is effective that the searchof the phase difference is performed by measuring the photoacousticsignal s₂ having the large signal amplitude as the phase basis.

In the case of the two-phase type phase sensitive amplifier, because thetype phase sensitive amplifier can has ability to always automaticallydetermine the phase difference θ, the phase difference can automaticallybe adjusted by utilizing the function. That is, the phase and amplitudeare determined by measuring the photoacoustic signal s₂ in the R−θ modein which unknown phase and amplitude can be measured, and the differencesignal s₁−s₂ of the photoacoustic signals is measured in the X measuringmode in which the amplitude can be measured while noise suppressionratio is improved by 3 dB when the phase is already known.

When the first semiconductor light source 801 emits the light, theoutput of about 10 nV is obtained at the output terminal 815 in the formof the electric signal Vd corresponding to the difference signal s₁−s₂of the photoacoustic signals. Then, the optical output of the firstsemiconductor light source 801 is set to zero again, and thephotoacoustic signal s₂ is measured while the sensitivity and timeconstant of the phase sensitive amplifier 814 are returned to theoriginal state, and the voltage of Vr=42 μV is obtained. The value of Vrbecomes 41 μV from the average of the two times of Vr.

As described above, it is desirable that the signal Vr corresponding tothe photoacoustic signal s₂ is measured twice before and after measuringthe difference signal s₁−s₂ of the photoacoustic signals. The drift ofthe unknown multiplier C can be corrected during measuring thedifference signal s₁−s₂ through the above procedure. The drift of theunknown multiplier C is derived from the change in distance r caused bythe change in pressing force of the fingertip of the subject and fromthe local temperature change caused by the light irradiation.

When the photoacoustic signal derived from the cholesterol in the livingbody test region is measured with the ultrasonic detector in the abovemeasuring system, the output value of several hundreds nV can beobtained as the difference signal s₁−s₂ of the photoacoustic signals.

Although the living body blood constituent concentration measuringapparatus and the living body control method of blood constituentconcentration measuring apparatus are described in the third example,the third example can also be applied to the liquid instead of theliving body. That is, as can be seen from the description of the directphotoacoustic method based on the first embodiment and the constituentconcentration computation method shown in the formula (4), the liquidconstituent concentration measuring apparatus and liquid constituentconcentration measuring apparatus controlling method according to thethird embodiment can also be realized to measuring objects except forthe living body. In this case, when the two wavelengths having the sameabsorption coefficient for the liquid and the different absorptioncoefficients for the object material are used, the constituent in theliquid can be detected without interruption of the absorption of theliquid. In the above embodiment and examples, fruit is placed instead ofthe living body test region, the liquid constituent concentrationmeasuring apparatus functions as a fruit sugar content meter. This isbecause sucrose and fruit sugar, which are of a sugar constituent of thefruit, has the absorption in the wavelength similar to the glucose whichis of the blood sugar constituent. Thus, the measuring apparatus andmeasuring apparatus controlling method according to the first embodimentcould clearly be applied to various objects without departing from thespirit of the first embodiment.

Fourth Example

FIG. 58 shows a configuration of a blood constituent concentrationmeasuring apparatus according to a fourth example. The fourth example isthe case where a contact thermometer 138 is further introduced to theblood constituent concentration measuring apparatus described in thefirst example-1 to the first example-4.

In the configuration shown in FIG. 58, the wavelength value of the firstlight source 101 is set at 1608 nm, and the wavelength of the secondlight source 105 is set at 1381 nm. These wavelengths are based on thewater absorbance at a water temperature of 39° C. as shown in FIG. 7.The reference temperature 39° C. is higher than an ordinary temperatureof the body temperature, and exactly it is necessary that the setting ofthe wavelength of the laser light source is changed according to thebody temperature of the subject, i.e., temperature of the living bodytest region 110. This is because the light absorption properties of thewater are changed depending on the water temperature.

FIG. 58 shows the water absorbance which depends on the watertemperature. FIG. 58 shows the absorbance of a water absorption bandhaving the maximum near the wavelength of 1450 nm for the watertemperature in the range of 25° C. to 55° C. at intervals of 5° C. whenthe water temperature is set at the parameter. As can be seen from FIG.58, the water absorption band is shifted toward the short wavelengthdirection as the water temperature rises, and thereby the absorption isincreased on the short wavelength side while the absorption is decreasedon the long wavelength side.

In order to check the detailed characteristics, FIG. 59 shows thetemperature change of the water absorbance at a constant wavelength. Onthe long wavelength side, the water absorbance is decreased at a rate of1.366×10⁻³ mm⁻¹/° C. for the temperature in the wavelength of 1608 nm ofthe first light source 101. On the other hand, on the short wavelengthside, the water absorbance is increased at a rate of 1.596×10⁻³ mm⁻¹/°C. in the wavelength of 1381 nm of the second light source 105.

As a result, the difference in absorbance between the two wavelengths isdecreased at a rate of 2.962×10⁻³ mm⁻¹/° C. for the temperature, and thespecific absorbance is decreased at a rate of 1.001×10⁻²/° C. for thetemperature. When the specific absorbance value of 0.114 M⁻¹ of theglucose at 1608 nm is used for the change rate, it is found thatunderestimate of 87.78 mM (1581 mg/dl) per deviation of 1/° C. isgenerated for the glucose concentration M from the reference temperatureof the body temperature.

In order correct to the error, the contact thermometer 138 is placed onthe light irradiation side of the living body test region 110 to measurethe local body temperature near the light irradiation portion, and thevalue in which the correction coefficient of 1581 mg/dl/° C. ismultiplied by the temperature difference between the measured bodytemperature value and the reference temperature is added to thecomputation value of the glucose concentration M by the formula (4). Thereason why the contact thermometer 138 is placed on the lightirradiation side is that the surface temperature on the irradiation sideof the living body test region where the light absorption is generatedis involved in the correction. For example, when the surface temperatureon the irradiation side is replaced by the living body surfacetemperature on the side which is contact with the side of the ultrasonicdetector 113, because the body surface temperature which is inunavoidable thermal contact with the ultrasonic detector 113 is used,there is a fear that the large error is generated.

In the case where the calibration test sample is used in the bloodconstituent concentration measuring apparatus shown in FIG. 57, thecorrection based on the surface body temperature measurement may beperformed as follows. FIG. 60 shows an example in which the calibrationtest sample is further applied to the blood constituent concentrationmeasuring apparatus shown in FIG. 57.

A thermometer 143, which measures the liquid temperature in thecalibration test sample 141, is attached to the calibration test sample141. In the above procedure, the scale reading of the thermometer isrecorded as a calibration temperature at the time when the photoacousticsignal outputted from the output terminal 115 becomes zero to fix theoutput the drive circuit 104. In the following measurement of the livingbody test region 110, the correction is performed using the calibrationtemperature instead of the reference temperature of the correctioncomputation method shown in the example. That is, the local bodytemperature near the light irradiation portion is measured by thecontact thermometer 138, and the value in which the correctioncoefficient of 1581 mg/dl/° C. is multiplied by the temperaturedifference between the measured body temperature value and thecalibration temperature may be added to the computation value of theglucose concentration M by the formula (4).

In the case where constant-temperature means (neglected in FIG. 60) forkeeping the liquid temperature constant is placed in the calibrationtest sample 141, in measuring the living body test region 110, thethermometer 143 placed in the calibration test sample 141 and thecontact thermometer 138 of the living body test region 110 aresimultaneously operated, and the temperature difference can also bedetermined from the difference in scale reading. Particularly, in thiscase, when the thermometer 143 and the contact thermometer 138 areformed by the same kind of thermometer, for example, a balanceconfiguration which accurately reads the difference in output betweenthe thermometer 143 and the contact thermometer 138 can be formed with abridge circuit. In the balance configuration, because the accuracy ofthe absolute temperature is not required for the thermometer 143 and thecontact thermometer 138, the example can be realized using a simpletemperature measuring device such as a thermistor.

Fifth Example

FIG. 61 shows a configuration of a blood constituent concentrationmeasuring apparatus according to a fifth example. The fifth example isthe case where the contact thermometer 138 is further introduced to theblood constituent concentration measuring apparatus described in thesecond example-1 to second example-3.

In the fifth example, because of the correction based on the surfacebody temperature measurement, it is preferable that the contactthermometer 138 is embedded in the surface of the acoustic coupler 142,which is in contact with the living body test region 110. In this case,it is desirable to use the contact thermometer 138 having the acousticimpedance close to the acoustic impedance of the acoustic coupler 142.This is because the disturbance of the ultrasonic wave propagation inthe acoustic coupler 142 by the contact thermometer 138 is suppressed.The following correction based on the surface body temperature valuemeasured by the contact thermometer 138 is performed by the samecomputation method as the fourth example. The calibration procedurewhich is performed by attaching the calibration test sample 141 insteadof the living body test region 110, the correction based on the surfacebody temperature value measured by the contact thermometer 138, and thelike can be performed according to the fourth example.

Second Embodiment

FIGS. 14 and 15 show a blood constituent concentration measuringapparatus according a second embodiment. In FIGS. 14 and 15, the numeral100 designates the oscillator, the numeral 101 designates the firstlight source, the numeral 102 designates the drive circuit, the numeral103 designates the oscillator, the numeral 105 designates the secondlight source, the numeral 116 designates the drive circuit, the numeral106 designates a third light source, the numeral 117 designates a drivecircuit, the numeral 118 designates a frequency divider, the numeral 119designates a 180°-phase shifter, the numeral 120 designates a coupler,the numeral 111 designates a living body test region, the numeral 121designates an ultrasonic detector, the numeral 122 designates a filter,the numeral 123 designates a synchronous detection amplifier, and thenumeral 124 designates a photoacoustic signal output terminal. Theoscillator 103, the drive circuit 102, and the first light source 101constitute a first irradiation unit which is of the light outgoingmeans. The oscillator 103, the 180°-phase shifter 119, the drive circuit116, and the second light source 105 constitute a second irradiationunit which is of the light outgoing means. The oscillator 100, the drivecircuit 117, and the third light source 106 constitute a thirdirradiation unit which is of the second light outgoing means. Theultrasonic detector 121 and the filter 122 constitute the acoustic wavedetection means.

In FIG. 14, the oscillator 103 oscillates at a constant frequency todetermine the frequency in which the first light source 101 and thesecond light source 105 are intensity modulated. The oscillator 100 isan oscillator which oscillates intermittently, and the oscillator 100determines a period during which the third light source 106 isintensity-modulated. The oscillator 100 may oscillate at a constantfrequency, or the oscillator 100 may oscillate at random times. Theoscillator 100 may intermittently oscillate at intervals longer than therepetition intervals of the constant frequency of the oscillator 103. Asa result, the third light source 106 is configured to be intensitymodulated at light emission repetition intervals longer than those ofthe first light source 101 and the second light source 105, and thethird light source 106 is also configured to be intensity modulated toan extent in which the photoacoustic signal is not generated.

The first light source 101, the second light source 105, and the thirdlight source 106 may be configured to be intensity modulated by the sameoscillator. For example, in FIG. 15, the oscillator 103 oscillates at aconstant frequency to determine the frequency in which the first lightsource 101, the second light source 105, and the third light source 106are intensity modulated. The frequency of the signal from the oscillator103 is divided by the frequency divider 118, which allows the thirdlight source 106 to oscillate periodically at intervals longer than therepetition intervals of the constant frequency in which the first lightsource 101 and the second light source 105 are intensity modulated.

The function and action of FIG. 14 are similar to those of FIG. 15except for the determination of the oscillation frequency of the thirdlight source, so that the description will be performed with referenceto FIG. 14. In FIG. 14, the signal from the oscillator 103 is inputtedto the drive circuit 102, and the drive circuit 102 drives the firstlight source 101. The signal from the oscillator 103 is inputted to the180°-phase shifter 119, and the signal is reversed. The reversed signalis inputted to the drive circuit 116, and the drive circuit 116 drivesthe second light source 105. The first light source 101 and the secondlight source 105 are intensity-modulated using the signals having thesame modulation frequency and reverse phases.

The first light source 101, the second light source 105, and the thirdlight source 106 are driven to emit the modulated light beams havingpredetermined wavelengths by the drive circuit 102, the drive circuit116, and the drive circuit 117 respectively. The coupler 120 multiplexesthe light beam from the first light source 101 and the light beam fromthe second light source 105, and the living body test region 111 whichis of the test subject is irradiated with the multiplexed light beam.When the configuration in which the light beam from the third lightsource 106 is also multiplexed is formed, the light can be focused onthe living body test region 111, so that the photoacoustic signal canefficiently be generated. Multiplexing the light beam from the firstlight source 101, the light beam from the second light source 105, andthe light beam from the third light source 106 can also be applied inthe first embodiment and the later-mentioned third embodiment, fourthembodiment, fifth embodiment, and sixth embodiment in addition to thesecond embodiment.

The ultrasonic detector 121 is placed in the surface opposite to thesurface irradiated with the multiplexed light beam from the coupler 120and the output light of the third light source 106 with respect to theliving body test region 111. The ultrasonic detector 121 receives theacoustic wave, i.e., the photoacoustic signal generated in the livingbody test region 111, the ultrasonic detector 121 converts thephotoacoustic signal into the electric signal proportional to theacoustic pressure, and the ultrasonic detector 121 outputs the electricsignal. The filter 122 passes the signal having the same frequency asthe oscillation frequency of the oscillator 103. The synchronousdetection amplifier 123 performs the synchronous detection of the signalinputted from the filter 122 using the synchronous signal inputted fromthe synchronous signal input terminal, and the synchronous detectionamplifier 123 outputs the amplitude of the synchronous-detectedultrasonic wave to the photoacoustic signal output terminal 124. Thesynchronous detection amplification enables the amplitude of theultrasonic wave to be detected from the photoacoustic signal with highsensitivity. The synchronous detection amplification performed by thesynchronous detection amplifier 123 can also be applied in the firstembodiment and the later-mentioned third embodiment, fourth embodiment,fifth embodiment, and sixth embodiment in addition to the secondembodiment.

At this point, it is defined that λ₁ is the light wavelength outputtedfrom the first light source 101, λ₂ is the light wavelength outputtedfrom the second light source 105, and λ₃ is the light wavelengthoutputted from the third light source 106. The absorption is generatedonly in the region having the large blood density by irradiating theliving body with the light having the wavelength λ₃, and the temperaturerises by the photothermal conversion. For example, the light having thewavelength of about 800 nm is used in a photo CT method, it is reportedthat the temperature is changed by about 0.1° C. inside the living body,and it is known that the temperature rise of about 0.1° C. is notharmful. The acoustic pressure P generated by the intermittent lightirradiation is expressed as follows.

$\begin{matrix}{P = {\frac{{\pi\beta}\; c}{2{Cp}}I}} & \left\lbrack {{Formula}\mspace{14mu} 14} \right\rbrack\end{matrix}$

Where I is irradiation light intensity, β is a thermal expansioncoefficient, c is sound velocity, and C_(p) is specific heat. In theabove parameters, only β and c depends on the temperature. Because thethermal expansion coefficient β is changed 3% per 1° C., thephotoacoustic signal is changed by about 0.3% by the temperature changeof 0.1° C. according to the formula (14). Because the photoacousticsignal is changed by 0.017% by the change amount of 5 mg/dL of glucose,the 20-fold signal change is generated by the temperature change of 0.1°C. The temperature rise by the simultaneous irradiation of the lighthaving the wavelength λ₃ increases the photoacoustic signal generated inthe region where the blood density is high.

The blood constituent computation method according to the secondembodiment will be described below with reference to the followingformula. When the absorption coefficients α₁ ^((b)), α₂ ^((b)) to whichthe background water mainly contributes and the molar absorptioncoefficients α₁ ⁽⁰⁾, α₂ ⁽⁰⁾ of the blood constituent are known eachother for the wavelengths λ₁ and λ₂, the concentration M is determinedby solving the formula (1) which is of the simultaneous equationsincluding the photoacoustic signal measured value s₁ and s₂ in thewavelengths.

Where C is a variable coefficient which is hardly controlled orcalculated, i.e., C is an unknown multiplier depending on the acousticcoupling, the ultrasonic detector sensitivity, the distance r betweenthe irradiation portion and the detection portion, the specific heat,the thermal expansion coefficient, the sound velocity, the modulationfrequency, and the absorption coefficient. When C is deleted in theformula (1), the formula (4) is obtained, and the concentration M can bedetermined from the photoacoustic signal s and the already knownabsorption coefficient α. However, in the formula (1), it is assumedthat the absorption coefficient α₁ ^((b)), α₂ ^((b)) to which thebackground water mainly contributes are substantially equal to eachother for the wavelengths λ₁ and λ₂. The formula (1) also has thefeature of s₁≅s₂.

In the method according to the second embodiment, the blood portiondiffers from the tissue portion such as the cuticle, the cell, and thefat in the acoustic generation amount of the water, so that the formula(1) is rewritten as follows.C _(b)(α₁ ^((b)) +Mα ₁ ⁽⁰⁾)+C _(t)α₁ ^((b)) =s ₁C _(b)(α₂ ^((b)) +Mα ₂ ⁽⁰⁾)+C _(t)α₂ ^((b)) =s ₂  [Formula 15]

Where C_(b) is an unknown coefficient in the blood and C_(t) is anunknown coefficient in the tissue such as the cuticle, the cell, and thefat. The photoacoustic signal generated in the region having the highblood density is amplified by the temperature change caused by thesimultaneous irradiation of the light beam having the wavelength λ₃.When A is an amplification rate, the formula (15) is rewritten asfollows.AC _(b)(α₁ ^((b)) +Mα ₁ ⁽⁰⁾)+C _(t)α₁ ^((b)) =s ₁₊AC _(b)(α₂ ^((b)) +Mα ₂ ⁽⁰⁾)+C _(t)α₂ ^((b)) =s ₂₊  [Formula 16]

When a difference between the formula (16) and the formula (15) isdetermined, the following formula (17) is obtained.(A−1)(α₁ ^((b)) +Mα ₁ ⁽⁰⁾)=s ₁₊ −s ₁ =Δs ₁(A−1)(α₂ ^((b)) +Mα ₂ ⁽⁰⁾)=s ₂₊ −s ₂ =Δs ₂  [Formula 17]Therefore, the water photoacoustic signal is removed from the tissuewhich is on the non-blood region.

At this point, when (A−1) is deleted in the formula (17), the followingformula is obtained.

$\begin{matrix}\begin{matrix}{M = \frac{\left( {{\Delta\; s_{1}} - {\Delta\; s_{2}}} \right)\alpha_{1}^{(b)}}{{\Delta\; s_{2}\alpha_{1}^{(0)}} - {\Delta\; s_{1}\alpha_{2}^{(0)}}}} \\{= {\frac{\alpha_{1}^{(b)}}{\alpha_{1}^{(0)} - \alpha_{2}^{(0)}}\frac{{\Delta\; s_{1}} - {\Delta\; s_{2}}}{\Delta\; s_{2}}}}\end{matrix} & \left\lbrack {{Formula}\mspace{14mu} 18} \right\rbrack\end{matrix}$Similarly to the formula (4), the concentration M can be determined fromthe difference acoustic signal Δs and the already known absorptioncoefficient α. However, in the formula (18), it is assumed that theabsorption coefficient α₂ ^((b)) to which the background water mainlycontributes are substantially equal to each other for the wavelengths λ₁and λ₂. The formula (18) also has the feature of Δs₁≅Δs₂.

In the second embodiment, not only the accuracy of the constituentconcentration computation is improved by the separation of the bloodconstituent, but also the background signal from the non-blood tissuecan be removed. In the non-blood tissue, the existence of glucose is sosmall that the glucose can be omitted, and the percentage of thephotoacoustic signal generation amount of total is large. Accordingly,when as compared with the conventional technique, the method of thesecond embodiment has the advantage that the background in which thetemperature change is expected in the tissue has no influence on themeasurement result.

FIG. 16 is a view showing a blood constituent computation methodaccording to the second embodiment. The measuring procedure in thesecond embodiment will be described in detail with reference to FIG. 15.The first light source 101 is intensity-modulated by the oscillator 103through the drive circuit 102, and the first light source 101 emits thelight having an output waveform 194 with the wavelength λ₁ as shown inthe upper part of FIG. 16. On the other hand, the second light source105 is intensity-modulated in synchronization with the first lightsource 101. The second light source 105 is modulated into the reversephase with respect to the first light source 101 by the 180°-phaseshifter 119, and thereby the second light source 105 emits the lighthaving an output waveform 195 with the wavelength λ2 as shown in theintermediate portion of FIG. 16. The third light source 106 isintensity-modulated in the frequency in which the oscillation frequencyof the oscillator 103 is divided by the frequency divider 118, and thethird light source 106 is intensity-modulated in synchronization withthe oscillator 103. The third light source 106 emits the light having anoutput waveform 196 with the wavelength λ₃ as shown in the lower part ofFIG. 16.

FIG. 17 is a view showing the photoacoustic signal measured by thesecond embodiment. The photoacoustic signal measured in the secondembodiment will be described with reference to FIG. 15. The two lightbeams having the mutually different wavelengths are multiplexed by thecoupler 120, and the living body test region 111 is irradiated with themultiplexed light. At this point, it is assumed that each of the lightbeams independently generates the acoustic wave. This is because thelinear superposition of the acoustic waves is already secured by thelinearity of the Helmholtz equation. Accordingly, an photoacousticsignal 197 is generated by the first light source (wavelength λ₁) asshown in the first stage of FIG. 17 and an photoacoustic signal 198 isgenerated by the second light source (wavelength λ₂) as shown in thesecond stage of FIG. 17. Further, a temperature change 199 is generatedby the third light source (wavelength λ₃) as shown in the third stage ofFIG. 17. Therefore, the photoacoustic signal is detected as acousticpressure by the ultrasonic detector 121, and the photoacoustic signalpasses through the filter 122. A summation 200 of the photoacousticsignal receives the modulation shown in the fourth stage of FIG. 17.

Δs₁:208 is obtained from the difference between a first peak value and asecond peak value in the summation 200 of the detected photoacousticsignal. Δs₂:209 is obtained from the difference between a first valleyvalue and a second valley value in the summation 200 of the detectedphotoacoustic signal, and the constituent concentration M can becomputed from the formula (17). Alternately, because the signalamplitude in the temperature rise corresponds to As₁−As₂ and the signalamplitude in the temperature fall corresponds to s₁−s₂, Δs₁−Δs₂ can beobtained by taking the difference between the signal amplitude in thetemperature rise and the signal amplitude in the temperature fall.Alternately, there is also a method of measuring the photoacousticsignal under the irradiation having the wavelength λ₁ or λ₂ in order toobtain the signals Δs₁ and Δs₂. In this case, the output of the secondlight source 105 is set to zero while the waveform of the first lightsource 101 is maintained.

This can be realized by blocking the light outputted from the firstlight source 101 or second light source 105 with a mechanical shutterbefore the input to the coupler 120 or by decreasing the output of thedrive circuit 102 or drive circuit 116 below the oscillation thresholdof the first light source 101 or second light source 105.

As described above, the third light source having the wavelength inwhich the hemoglobin of the blood constituent existing only in the bloodexhibits the characteristic absorption with respect to the first lightsource and the second light source is added to perform the measurementusing the modulation frequency in which the photoacoustic signal is notgenerated. Therefore, the temperature rise is generated in the regionwhere the blood density is high by the blood absorption, and thephotoacoustic signal generated from the change in sound velocity isincreased. As a result, the change in photoacoustic signal correspondsto the temperature change of the blood, and the photoacoustic signalgenerated in the blood region can be increased. Accordingly, thetemperature change can separately be generated only in the blood regionwithout directly imparting the pressure to the living body, so that theblood region can efficiently be determined. The second embodiment is atechnique of being able to reproducing the separation of the bloodregion and the non-blood region in the noninvasive manner.

Although the living body blood constituent concentration measuringapparatus and living body control method of blood constituentconcentration measuring apparatus are described in the secondembodiment, the second embodiment can also applied to the liquid insteadof the living body. That is, the blood constituent concentrationmeasuring apparatus and control method of blood constituentconcentration measuring apparatus according to the second embodiment canalso be realized for the measuring objects other than the living body.In this case, when the two wavelengths having the same absorptioncoefficient for the liquid and the different absorption coefficients forthe object material are used, the constituent in the liquid can bedetected without interruption of the absorption of the liquid. In theabove embodiment and examples, fruit is placed instead of the livingbody test region, the liquid constituent concentration measuringapparatus and the control method of liquid constituent concentrationmeasuring apparatus function as the fruit sugar content meter. This isbecause the sucrose and fruit sugar, which are of the sugar constituentof the fruit, has the absorption in the wavelength similar to theglucose which is of the blood sugar constituent. Thus, the measuringapparatus and measuring apparatus controlling method according to thefirst embodiment could clearly be applied to various objects withoutdeparting from the spirit of the first embodiment.

EXAMPLES

Specific examples in the second embodiment will be described below.

First Example

FIG. 18 shows configurations of the blood constituent concentrationmeasuring apparatus and control method of blood constituentconcentration measuring apparatus according to the first example. InFIG. 18, the numeral 523 designates a first semiconductor light source,the numeral 524 designates a drive current source, the numeral 525designates an oscillator, the numeral 526 designates a lens, the numeral527 designates a second semiconductor light source, the numeral 528designates a drive current source, the numeral 529 designates a180°-phase shifter, the numeral 530 designates a lens, the numeral 531designates a coupler, the numeral 532 designates a third semiconductorlight source, the numeral 533 designates a drive current source, thenumeral 534 designates a frequency divider, the numeral 535 designates alens, the numeral 536 designates a coupler, the numeral 537 designates aliving body test region, the numeral 516 designates an acoustic lens,the numeral 517 designates an acoustic matching device, the numeral 518designates an ultrasonic detector, the numeral 519 designates a highpass filter, the numeral 520 designates a synchronous detectionamplifier, the numeral 521 designates a photoacoustic signal outputterminal, and the numeral 522 designates a temperature measurementdevice.

In FIG. 18, the oscillator 525 oscillates at a constant frequency todetermine the frequency in which the first semiconductor light source523 and the second semiconductor light source 527 are intensitymodulated. The frequency of the signal from the oscillator 525 isdivided by the frequency divider 534, and thereby the thirdsemiconductor light source 532 periodically oscillates at intervalslonger than the repetition interval of the constant frequencies in whichthe first semiconductor light source 523 and the second semiconductorlight source 527 are intensity modulated.

The signal from the oscillator 525 is inputted to the drive currentsource 524, and the drive current source 524 drives the firstsemiconductor light source 523. The signal from the oscillator 525 isinputted to the 180°-phase shifter 529, and the signal is reversed.

The reversed signal is inputted to the drive current source 528, and thedrive current source 528 drives the second semiconductor light source527. The first semiconductor light source 523 and the secondsemiconductor light source 527 are intensity-modulated using the signalshaving the same modulation frequency and reverse phases.

The first semiconductor light source 523, the second semiconductor lightsource 527, the third semiconductor light source 532 are driven by thedrive current source 524, the drive current source 528, and the drivecurrent source 533 respectively. The first semiconductor light source523, the second semiconductor light source 527, the third semiconductorlight source 532 output the modulated light beams having thepredetermined wavelengths respectively. The light from the firstsemiconductor light source 523 is converted into the beam by the lens526, the light from the second semiconductor light source 527 isconverted into the beam by the lens 530, and the beams are multiplexedinto one beam by the coupler 531. The light from the third semiconductorlight source 532 is converted into the beam by the lens 535, and thecoupler 536 further multiplexes the beam and the beam from the coupler531. The living body test region 537, which is of the test subject, isirradiated with multiplexed beam. As described above, multiplexing thelight beam from the first light source 523, the light beam from thesecond light source 527, and the light beam from the third semiconductorlight source 532 can also be applied in the first embodiment and thelater-mentioned third embodiment, fourth embodiment, fifth embodiment,and sixth embodiment in addition to the first example.

The temperature measurement device 522 is placed near the living bodytest region 537 irradiated with the output light of the coupler 536, thetemperature change of the living body test region 537 generated by thelight of the third semiconductor light source 532 is detected, theoutput of the temperature measurement device 522 is inputted to acontrol terminal of the drive current source 533, and drive current ofthe drive current source 533 is adjusted such that the temperaturechange of the living body test region 537 becomes the desired value.

The acoustic lens 516, the acoustic matching device 517, and theultrasonic detector 518 are placed while coming into contact with thesurface opposite to the surface of the living body test region 537irradiated with the light beam from the coupler 536. The acoustic lens516 focuses the acoustic wave, i.e., the photoacoustic signal generatedin the living body test region 537, and the acoustic lens 516efficiently transmits the photoacoustic signal to the ultrasonicdetector 518 through the acoustic matching device 517. The acousticmatching device 517 enhances the transmission efficiency between theacoustic lens 516 and the ultrasonic detector 518. The ultrasonicdetector 518 receives the photoacoustic signal generated in the livingbody test region 537, and the ultrasonic detector 518 converts thephotoacoustic signal into the electric signal proportional to theacoustic pressure to output the electric signal. The high pass filter519 passes the signal having the same frequency as the oscillationfrequency of the oscillator 525. The synchronous detection amplifier 520performs the synchronous detection of the signal inputted from the highpass filter 519 using the synchronous signal inputted from thesynchronous signal input terminal, and the synchronous detectionamplifier 520 outputs the amplitude of the synchronous-detectedphotoacoustic signal to the photoacoustic signal output terminal 521.

In the above configuration, the wavelength of the first semiconductorlight source 523 is set at 1380 nm, the wavelength of the secondsemiconductor light source 527 is set at 1608 nm, and the wavelength ofthe third semiconductor light source 532 is set at 800 nm. The firstsemiconductor light source 523 and the second semiconductor light source527 are intensity-modulated in the modulation frequency of 200 kHz. Thetemperature rise is 2° C. or less which is not harmful to the humanbody. Accordingly, the maximum allowable temperature is 39° C. when theinitial temperature is set at 37° C. For example, in consideration of athermal diffusion coefficient of the living body, in order to generatethe temperature modulation in the range of 0.1 to 0.2° C. in the livingbody, a frequency dividing rate of the frequency divider is set suchthat the modulation frequency of the third semiconductor light source532 is set to 100 Hz or less. Because the modulation frequency whichgenerates the desired temperature change depends on the wavelength andthe beam diameter of the light source, it is necessary that theadjustments including the light source output are performed while atemperature measurement device and the photoacoustic signal intensityare observed. However, in order to shorten the measurement time to theminimum, it is effective that the output light of the thirdsemiconductor light source 532 is coaxial with the output light beams ofthe first semiconductor light source 523 and second semiconductor lightsource 527 to select and adjust the lens 535 such that the beamdiameters are equal to one another. In consideration of the aboveconditions, the light source output is set at 5 mW. The lens 526, thelens 530, and the lens 535 are adjusted to set the beam diameters at 3mm respectively. Equalizing the beam diameters of the firstsemiconductor light source 523 and second semiconductor light source 527can also be applied in the first embodiment and the later-mentionedthird embodiment, fourth embodiment, fifth embodiment, and sixthembodiment in addition to the second embodiment.

The photoacoustic signal from the living body, which is generated byirradiating the living body test region 537 with the light reaches theultrasonic detector 518 through the acoustic lens 516 and the acousticmatching device 517. The acoustic lens 516, which focuses the ultrasonicwave into a central portion of the ultrasonic detector 518, is made of amaterial having the acoustic impedance close to the living body. Forexample, the acoustic lens 516 is made of silicone. The acousticmatching device 517 is made of the material having the acousticimpedance which is substantially located at the midpoint between theacoustic impedances of the acoustic lens 516 and ultrasonic detector518. For example, the acoustic matching device 517 is made of acryl. Theultrasonic detector 518 is a piezoelectric device or a capacitormicrophone which is designed to have a natural frequency similar to themodulation frequencies of the first semiconductor light source 523 andthe second semiconductor light source 527. The photoacoustic signal isconverted into the electric signal by the ultrasonic detector 518, andthe amplitude of the ultrasonic wave is detected by the synchronousdetection amplifier 520.

When the first semiconductor light source 523 is blocked, namely, in thecase of only the second semiconductor light source 527, the output levelof the synchronous detection amplifier 520 is about 20 μV. When thefirst semiconductor light source 523 and the second semiconductor lightsource 527 simultaneously emit the light beams while the thirdsemiconductor light source 532 is blocked, the output level of thesynchronous detection amplifier 520 is about 5 nV. Further, the thirdsemiconductor light source 532 is added, and the signal is detectedwhile the temperature modulation is performed. The output level of thesynchronous detection amplifier 520 is 5.37 nV in the temperature rise.The output level of the synchronous detection amplifier 520 is 5.33 nVin the temperature fall.

Δs₁−Δs₂ in the formula (18) becomes 42.1 pV from the difference betweenthe output levels. Δs₂ of 60.3 nV is determined by reading thedifference between the valley value in the temperature rise and thevalley value in the temperature fall using, e.g., an oscilloscope. Thus,the glucose concentration M of 3 mM (50 mg/dL) is determined from theformula (18) using the already known specific absorbance value 0.114 M⁻¹in 1608 nm.

The blood constituent concentration measurement described in the firstexample is the forward propagation type in which the photoacousticsignal is measured in the surface opposite to the surface irradiatedwith the light with respect to the living body test region 537. On theother hand, the rearward propagation type in which the photoacousticsignal is measured in the same surface as the surface irradiated withthe light with respect to the living body test region 537 can also beconfigured, and the operation of the rearward propagation type issimilar to the frontward propagation type.

Although the living body blood constituent concentration measuringapparatus and living body control method of blood constituentconcentration measuring apparatus are described in the first example,the first example can also applied to the liquid instead of the livingbody. That is, the blood constituent concentration measuring apparatusand control method of blood constituent concentration measuringapparatus according to the first example can also be realized for themeasuring objects other than the living body. In this case, when the twowavelengths having the same absorption coefficient for the solvent andthe different absorption coefficients for the constituent in the liquidare used, the constituent in the liquid can be detected withoutinterruption of the absorption of the solvent.

Second Example

FIG. 19 shows a second example in which the inventions of bloodconstituent concentration measuring apparatus and the control method ofblood constituent concentration measuring apparatus according to thesecond embodiment is used for liquid constituent analysis. Liquid foodsand beverages to which sugars are added can be cited as an example ofthe liquid sample. In FIG. 19, the numeral 701 designates a firstsemiconductor light source, the numeral 702 designates a drive currentsource, the numeral 703 designates an oscillator, the numeral 704designates a lens, the numeral 705 designates a second semiconductorlight source, the numeral 706 designates a drive current source, thenumeral 707 designates a 180°-phase shifter, the numeral 708 designatesa lens, the numeral 709 designates a coupler, the numeral 710 designatesa third semiconductor light source, the numeral 711 designates a drivecurrent source, the numeral 712 designates a frequency divider, thenumeral 713 designates a lens, the numeral 714 designates a coupler, thenumeral 715 designates a liquid sample, the numeral 716 designates asample cell, the numeral 717 designates an acoustic matching device, thenumeral 718 designates an ultrasonic detector, the numeral 719designates a high pass filter, the numeral 720 designates a synchronousdetection amplifier, the numeral 721 designates a photoacoustic signaloutput terminal, and the numeral 722 designates a temperaturemeasurement device.

For the purpose of avoidance of overlap, the components in the secondexample different from the first example of the blood constituentconcentration measuring apparatus and control method of bloodconstituent concentration measuring apparatus shown in FIG. 18 will bemainly described.

The liquid sample 715 is irradiated with the light multiplexed by thecoupler 714. The temperature measurement device 722 is placed in thesample cell 716 near the region irradiated with the output light of thecoupler 714, and the output terminal of the temperature measurementdevice 722 is connected to the control terminal of the drive currentsource 711 through the signal line. The temperature measurement device722 has the function of measuring the temperature of the liquid sample715 to output the measurement result to the output terminal in the formof the electric signal.

The acoustic matching device 717 is placed while coming into contactwith the surface opposite to the surface of the sample cell 716irradiated with the output light of the coupler 714. The ultrasonicdetector 718 is placed through the acoustic matching device 717. Theacoustic matching device 717 has the function of enhancing thephotoacoustic signal transmission efficiency between the sample cell 716and the ultrasonic detector 718.

In the second example, the measuring object is a sugar concentrationcontained in a food solution in which a fat content and water are mixedtogether. Because the sugar concentration contained only in the fatcontent of the mixed solution in which the fat content and water aremixed, in FIG. 19, the wavelength of the first semiconductor lightsource 701 is set at 1380 nm, the wavelength of the second semiconductorlight source 705 is set at 1608 nm, and the wavelength of the thirdsemiconductor light source 710 is set at 1710 nm in which the fatcontent exhibits the remarkable absorption.

The modulation frequencies of the first semiconductor light source 701and the second semiconductor light source 705 are set at 200 kHz. Inconsideration of a thermal diffusion coefficient of liquid, thefrequency dividing rate of the frequency divider 712 is set such thatthe temperature modulation is generated in the range of 0.1 to 0.2° C.in the liquid, and the modulation frequency of the third semiconductorlight source 710 is set to 100 Hz or less. Actually, because themodulation frequency which generates the desired temperature changedepends on the wavelength and the beam diameter of the light source, theadjustments including the light source output is performed while thetemperature measured by the temperature measurement device 722 and thephotoacoustic signal intensity are observed.

In order to shorten the measurement time, it is effective that theoutput light of the third semiconductor light source 710 is coaxial withthe output light beams of the first semiconductor light source 701 andthe second semiconductor light source 705 to select and adjust the lens713 such that the beam diameters are equal to one another.

In consideration of the above conditions, the light source outputs ofthe first semiconductor light source 701, the second semiconductor lightsource 705, and the third semiconductor light source 710 are set at 12mW. The lens 704, the lens 708, and the lens 713 are adjusted to set thebeam diameters of the first semiconductor light source 701, the secondsemiconductor light source 705, and the third semiconductor light source710 at 4 mm respectively.

When the liquid sample 715 is irradiated with the irradiation lightbeams from the first semiconductor light source 701, the secondsemiconductor light source 705, and the third semiconductor light source710, the acoustic wave, i.e., the photoacoustic signal generated in theliquid sample 715 reaches the ultrasonic detector 718 through the samplecell 716 and the acoustic matching device 717. The acoustic matchingdevice 717 is made of the material such as aluminum having the acousticimpedance which is substantially located at the midpoint between theacoustic impedances of the sample cell 716 such as glass and theultrasonic detector 718 such as ceramic.

An acoustic matching agent is applied between the sample cell 716 andthe acoustic matching device 717 and between the acoustic matchingdevice 717 and the ultrasonic detector 718 to reduce the influence ofthe reflection due to the existence of an air layer. The ultrasonicdetector 718 is the piezoelectric device or capacitor microphone whichis designed to have the natural frequency similar to the modulationfrequencies of the first semiconductor light source 701 and the secondsemiconductor light source 705. The photoacoustic signal is convertedinto the electric signal by the ultrasonic detector 718, and theelectric signal passes through the high pass filter 719. At this point,the blocking frequency and the time constant are set such that theelectric signal is not attenuated near 200 kHz, but attenuated in 1 kHzby 20 dB or more.

The electric signal outputted from the high pass filter 719 is detectedby the synchronous detection amplifier 720. When the output of the firstsemiconductor light source 701 is blocked, namely, in the case of onlythe second semiconductor light source 705, the output of the synchronousdetection amplifier 720 is about 120 RV. When the first semiconductorlight source 701 and the second semiconductor light source 705simultaneously emit the light beams while the output of the thirdsemiconductor light source 710 is blocked, the obtained output of thesynchronous detection amplifier 720 is about 12 nVp-p. Further, thethird semiconductor light source 710 is added, and the temperaturemodulation is performed. The output of the synchronous detectionamplifier 720 is 4.33 μVp-p in the temperature rise. The output of thesynchronous detection amplifier 720 is 4.36 μVp-p in the temperaturefall. In the formula (18), Δs₁−Δs₂ becomes 30 nV from the differencebetween the outputs.

In the second example, Δs₂ of 5.4 μV is determined by reading thedifference between the valley value in the temperature rise and thevalley value in the temperature fall using, e.g., the oscilloscope.

As a result, the glucose concentration M of 45 mM (750 mg/dL) isdetermined from the formula (18) using the already known specificabsorbance value 0.114 M⁻¹ in the wavelength of 1608 nm.

The blood constituent concentration measurement described in the secondexample is the forward propagation type in which the photoacousticsignal is measured in the surface opposite to the light irradiationsurface with respect to the liquid sample 715. On the other hand, therearward propagation type in which the photoacoustic signal is measuredin the same surface as the surface irradiated with the light withrespect to the liquid sample 715 can also be configured, and theoperation of the rearward propagation type is similar to the frontwardpropagation type.

In the above configuration of the invention in the embodiment andexamples, the fruit is placed instead of the liquid sample, the liquidconstituent concentration measuring apparatus functions as the fruitsugar content meter. This is because the sucrose and the fruit sugar,which are of the sugar constituent of the fruit, has the absorption inthe wavelength similar to the glucose which is of the blood sugarconstituent.

Third Embodiment

A blood constituent concentration measuring apparatus of a thirdembodiment is a blood constituent concentration measuring apparatusincluding light generating means for generating light; frequency sweepmeans for sweeping a modulation frequency, the light generated by thelight generating means being modulated in the modulation frequency;light modulation means for electrically intensity-modulating the lightusing a signal from the frequency sweep means, the light being generatedby the light generating means; light outgoing means for outputting theintensity-modulated light toward the living body; acoustic wavedetection means for detecting an acoustic wave which is generated in theliving body by the outputted light; and integration means forintegrating the acoustic wave in a swept modulation frequency range, theacoustic wave being detected by the acoustic wave detection means.

The blood constituent concentration measuring apparatus according to thethird embodiment will be described with reference to FIG. 20. Aconfiguration example of the blood constituent concentration measuringapparatus of the third embodiment shown in FIG. 20 includes a lightsource 112 which is of the light generating means, a lens 99 which is ofthe light outgoing means, a drive circuit 104 and an oscillator 103which are of the modulation means, a control circuit 125 which is of thefrequency sweep means, an acoustic coupler 126, an ultrasonic detector127, and a phase sensitive amplifier 128 which are of the acoustic wavedetection means, and a computing device 129 which is of the integrationmeans.

The oscillator 103 is connected to the drive circuit 104, the phasesensitive amplifier 128, and the control circuit 125 through the signallines. The oscillator 103 transmits the oscillation signal to the drivecircuit 104 and the phase sensitive amplifier 128 respectively, and theoscillator 103 receives the signal which controls the sweep of theoscillation frequency from the control circuit 125.

The drive circuit 104 receives the signal transmitted from theoscillator 103. The drive circuit 104 supplies the drive electric powerto the light source 112, connected to the drive circuit 104 through thesignal line, to cause the light source 112 to emit the light. The drivecircuit 104 intensity-modulates the light outputted from the lightsource 112 in synchronization with the oscillation frequency of theoscillator 103. The light wavelength outputted from the light source 112is set at the wavelength in which the blood constituent of the measuringobject in the living body exhibits the absorption.

The light emitted from the light source 112 passes through the lens 99,a predetermined position of the living body test region 110 isirradiated with the light, and the photoacoustic signal is generated inthe living body test region 110.

The ultrasonic detector 127 detects the acoustic wave generated in theliving body test region 110 through the acoustic coupler 126, theultrasonic detector 127 converts the acoustic wave into the electricsignal proportional to the magnitude of the detected acoustic wave, andthe ultrasonic detector 127 transmits the electric signal to the phasesensitive amplifier 128 connected to the ultrasonic detector 127 throughthe signal line. At this point, one of surfaces of the acoustic coupler126 is in contact with the living body test region 110, and the othersurface is in contact with the ultrasonic detector 127, and thereby theacoustic coupler 126 has the function of efficiently transmitting thephotoacoustic signal generated in the living body test region 110 to theultrasonic detector 127.

The phase sensitive amplifier 128 receives the signal transmitted fromthe oscillator 103 to form the synchronous signal for the synchronousdetection, and the phase sensitive amplifier 128 receives the electricsignal proportional to the magnitude of the photoacoustic signaltransmitted from the ultrasonic detector 127. The phase sensitiveamplifier 128 performs the synchronous detection, the amplification, andthe filtering to the electric signal, and the phase sensitive amplifier128 transmits the electric signal to the computing device 129 connectedto the phase sensitive amplifier 128 through the signal line.

The computing device 129 receives the signal transmitted from the phasesensitive amplifier 128, and the computing device 129 integrates thereceived signal in the oscillation frequency range which is receivedfrom the control circuit 125 and swept by the oscillator 103. Then, fromthe detection result of the integrated photoacoustic signal, thecomputing device 129 selects the detection value in the resonancefrequency in which the detection sensitivity of the ultrasonic detector127 is increased, and the computing device 129 integrates the selectedvalue. At this point, the blood constituent concentration of themeasuring object can be computed from the integrated detection valueusing the computing device 129 or an external device (not shown).

The computing device 129 receives the signal transmitted from the phasesensitive amplifier 128, the computing device 129 transmits the receivedsignal and the control signal to the control circuit 125 connected tothe computing device 129 through the signal line. The control signalcontrols the oscillator 103 from the oscillation frequency which isswept by the oscillator 103 and received from control circuit 125 suchthat the oscillation frequency of the oscillator 103, i.e., the sweeprange of the modulation frequency includes the range of the change inresonance frequency of the ultrasonic detector 127.

In an example of the sensitivity characteristics of the ultrasonicdetector shown in FIG. 21, for example, the computing device 129 maytransmit the signal for controlling the sweep of the oscillationfrequency of the oscillator 103 to the control circuit 125 such that themodulation frequency of the light source 112 is swept in the rangebroader than the frequency of a half-value width of the resonancecharacteristics. The computing device 129 may also transmit the signalfor controlling the sweep of the oscillation frequency of the oscillator103 to the control circuit 125 such that the modulation frequency of thelight source 112 is swept in the frequency range of a fraction of thepeak value of the resonance characteristics, e.g., a half of the peakvalue. The control circuit 125 controls the oscillation frequency of theoscillator 103 according to the control signal transmitted from thecomputing device 129.

As described above, in the blood constituent concentration measuringapparatus of the third embodiment, even if the resonance characteristicsof the ultrasonic detector 127 is changed, the modulation frequency ofthe light with which the living body is irradiated is swept to detectthe photoacoustic signal in the living body. Therefore, the value, whichis detected with high sensitivity in association with the resonancefrequency of the ultrasonic detector 127, is selected from the detectionvalues of the photoacoustic signal, and the value is integrated, whichallows the blood constituent concentration to be correctly measured.

A control method of blood constituent concentration measuring apparatusof the third embodiment is a control method of blood constituentconcentration measuring apparatus sequentially including a lightgenerating procedure in which light generating means generates light; afrequency sweep procedure in which frequency sweep means sweeps amodulation frequency, the light generated in the light generatingprocedure being modulated in the modulation frequency; a lightmodulation procedure in which light modulation means electricallyintensity-modulates the light using a signal swept in the frequencysweep procedure, the light being generated in the light generatingprocedure; a light outgoing procedure in which light outgoing meansoutputs the light toward living body; the light beingintensity-modulated in the light modulation procedure; an acoustic wavedetection procedure in which acoustic wave detection means detects anacoustic wave, i.e., an photoacoustic signal which is generated in theliving body by the light outputted in the light outgoing procedure; andan integration procedure in which integration means integrates theacoustic wave in a swept modulation frequency range, the acoustic wavebeing detected in the acoustic wave detection procedure.

In the control method of blood constituent concentration measuringapparatus of the third embodiment, the control circuit 125 shown in FIG.20 controls the frequency, the output of the oscillator 103 which isswept in the oscillation frequency is transmitted to the drive circuit104, the drive circuit 104 which receives the swept frequency drives thelight source 112 including, e.g., the semiconductor laser to cause togenerate the light, and the light is intensity-modulated. In this case,the light source 112 generates the light, and the generated light can beintensity-modulated by the swept frequency. At this point, the lightwavelength generated by the light source 112 is set at the wavelength inwhich the blood constituent of the measuring object exhibits theabsorption.

As described above, the living body is irradiated with theintensity-modulated light, the photoacoustic signal generated in theliving body by the intensity-modulated light is detected by theultrasonic detector 127 through the acoustic coupler 126 shown in FIG.20, the photoacoustic signal is converted into the electric signalproportional to the magnitude of the photoacoustic signal, thesynchronous detection, the amplification, and the filtering areperformed to the electric signal by the phase sensitive amplifier 128,the electric signals are integrated for a predetermined time andaveraged, and the electric signal is transmitted to the computing device129.

As described above, the detected photoacoustic signals are integrated asthe electric signals proportional to the pressure in the modulationfrequency range which is swept by the computing device 129 shown in FIG.20, the detection value or frequency in the resonance frequency wherethe detection sensitivity is increased is selected from the integratedelectric signals proportional to the magnitude of the photoacousticsignal, and the integration is performed in the selected frequency rangeto compute the blood constituent concentration.

According to the above method, even if the resonance frequency of theultrasonic detector 127, which detects the photoacoustic signal in theliving body, is changed, the detection values of the photoacousticsignals can be selected and integrated in the frequency corresponding tothe resonance frequency of the ultrasonic detector 127 to compute theblood constituent concentration. Therefore, the blood constituentconcentration can correctly be measured.

A blood constituent concentration measuring apparatus of the thirdembodiment is a blood constituent concentration measuring apparatusincluding light generating means for generating two light beams havingdifferent wavelengths; frequency sweep means for sweeping a modulationfrequency, the light generated by the light generating means beingmodulated in the modulation frequency; light modulation means forelectrically intensity-modulating each of the two light beams having themutually different wavelengths using signals having reverse phases wherethe signals are swept in the frequency sweep means; light outgoing meansfor multiplexing into one light flux to output the twointensity-modulated light beams having the mutually differentwavelengths toward a living body; acoustic wave detection means fordetecting an acoustic wave i.e., a photoacoustic signal generated in theliving body by the outputted light; and integration means forintegrating the acoustic wave in a swept modulation frequency range, theacoustic wave being detected by the acoustic wave detection means.

In the blood constituent concentration measuring apparatus of the thirdembodiment, the light generating means can set one of the lightwavelengths at the wavelength in which the blood constituent exhibitsthe characteristic absorption, and the light generating means can setthe other light wavelength at the wavelength in which the water exhibitsthe absorption similar to that in one of the light wavelengths.

A configuration of the blood constituent concentration measuringapparatus of the third embodiment will be described with reference toFIG. 22. The blood constituent concentration measuring apparatus of thethird embodiment includes a first light source 301 and a second lightsource 302 which are of the light generating means, a coupler 308 whichis of the light outgoing means an oscillator 298, a drive circuit 303, adrive circuit 297, and a 180°-phase shifter 299 which are of themodulation means, a control circuit 300 which is of the frequency sweepmeans, an acoustic coupler 327, an ultrasonic detector 328, and a phasesensitive amplifier 329 which are of the acoustic wave detection means,and a computing device 330 which is of the integration means.

The oscillator 298 is connected to the drive circuit 303, the 180°-phaseshifter 299, the phase sensitive amplifier 329, and the control circuit300 through the signal lines respectively. The oscillator 298 transmitsthe oscillation signal to the drive circuit 303, the 180°-phase shifter299, and the phase sensitive amplifier 329 respectively, and theoscillator 298 receives the signal which controls the sweep of theoscillation frequency from the control circuit 300.

The drive circuit 303 receives the signal transmitted from theoscillator 298. The drive circuit 303 supplies the drive electric powerto the first light source 301, connected to the drive circuit 303through the signal line, to cause the first light source 301 to emit thelight. Then, the drive circuit 303 intensity-modulates the lightoutputted from the first light source 301 in synchronization with theoscillation frequency of the oscillator 298.

The 180°-phase shifter 299 receives the signal transmitted from theoscillator 298, and the 180°-phase shifter 299 transmits the signal inwhich the 180°-phase change is imparted to the received signal to thedrive circuit 297 connected to the 180°-phase shifter 299 through thesignal line.

The drive circuit 297 receives the signal transmitted from the180°-phase shifter 299. The drive circuit 297 supplies the driveelectric power to the second light source 302, connected to the drivecircuit 297 through the signal line, to cause the second light source302 to emit the light. The drive circuit 297 intensity-modulates thelight outputted from the second light source 302 in synchronization withthe signal in which the 180°-phase change is imparted to the oscillationfrequency of the oscillator 298. Accordingly, the light beams outputtedfrom the first light source 301 and the second light source 302 aremodulated using the opposite-phase signals each other.

For the wavelengths of the first light source 301 and second lightsource 302 shown in FIG. 22, one of the light wavelengths is set at thewavelength in which the blood constituent set as the measuring objectexhibits the characteristic absorption, and the other light wavelengthis set at the wavelength in which the water exhibits the absorptionsimilar to that in one of the light wavelengths.

The first light source 301 and the second light source 302 emit thelight beams having the different wavelengths as described above, thelight beams outputted from the first light source. 301 and second lightsource 302 are inputted to the coupler 308 connected to the first lightsource 301 and the second light source 302 by the light wavetransmission means respectively.

The light beam outputted from the first light source 301 and the lightbeam outputted from the second light source 302 are inputted to thecoupler 308, and the light beams are multiplexed into one light flux.Then, the predetermined position of the living body test region 309 asthe test subject is irradiated with the light flux, and the acousticwave, i.e., the photoacoustic signal is generated in the living bodytest region 309.

The ultrasonic detector 328 detects the photoacoustic signal generatedin the living body test region 309 through the acoustic coupler 327, theultrasonic detector 328 converts the photoacoustic signal into theelectric signal proportional to the magnitude of the photoacousticsignal, and the ultrasonic detector 328 transmits the electric signal tothe phase sensitive amplifier 329 connected to the ultrasonic detector328 through the signal line.

The wavelengths of the first light source 301 and the second lightsource 302 are set at the light wavelengths in which the difference inabsorption exhibited by the blood constituents set as the measuringobject is larger than the difference in absorption exhibited by thewater. Alternatively, the difference in absorption exhibited by thewater may be set to zero, and one of the light wavelengths may be set atthe wavelength in which the blood constituent set as the measuringobject exhibits the characteristic absorption, and the other lightwavelength may be set at the wavelength in which the water exhibits theabsorption similar to that in one of the light wavelengths. It isdesirable that the wavelengths of the first light source 301 and thesecond light source 302 are set at the wavelengths in which thedifference in absorption exhibited by the blood constituents set as themeasuring object is larger than the difference in absorption exhibitedby other blood constituents except for the blood constituents set as themeasuring object. Setting the wavelengths of the first light source 301and the second light source 302 at the above values can also be appliedin the first embodiment, the second embodiment, and the later-mentionedthird embodiment, fourth embodiment, fifth embodiment, and sixthembodiment in addition to the third embodiment.

Because the light beams outputted from the first light source 301 andthe second light source 302 are modulated in the reverse phases, thephotoacoustic signal generated in the living body test region 309 by thelight beam in which the light beams outputted from first light source301 and the second light source 302 are multiplexed is detected by theultrasonic detector 328 as the difference in magnitude of thephotoacoustic signals. At the stage of the photoacoustic signal, thephotoacoustic signal which is generated by the absorptions of the waterand the blood constituent set as the measuring object for themultiplexed light with which the living body test region 309 isirradiated and the photoacoustic signal which is generated only by theabsorption of the water are superposed to each other in the differencein magnitude of the photoacoustic signals

One of the surfaces of the acoustic coupler 327 is in contact with theliving body test region 309, the other surface is in contact with theultrasonic detector 328, and the acoustic coupler 327 has the functionof efficiently transmitting the photoacoustic signal generated in theliving body test region 309 to the ultrasonic detector 328.

The phase sensitive amplifier 329 receives the signal transmitted fromthe oscillator 298 to form the synchronous signal for the synchronousdetection, and the phase sensitive amplifier 329 receives the electricsignal proportional to the magnitude of the photoacoustic signaltransmitted from the ultrasonic detector 328. The phase sensitiveamplifier 329 performs the synchronous detection, the amplification, andthe filtering to the electric signal, and the phase sensitive amplifier329 transmits the electric signal to the computing device 330 connectedto the phase sensitive amplifier 329 through the signal line.

The computing device 330 receives the signal transmitted from the phasesensitive amplifier 329, and the computing device 330 integrates thereceived signal in the oscillation frequency range which is receivedfrom the control circuit 300 and swept by the oscillator 298. Then, fromthe detection result of the integrated photoacoustic signal, thecomputing device 330 selects the detection value in the resonancefrequency in which the detection sensitivity of the ultrasonic detector328 is increased, and the computing device 330 integrates the selectedvalue and the blood constituent concentration is computed. At thispoint, the blood constituent concentration of the measuring object canbe computed from the integrated detection value using the computingdevice 330 or an external device (not shown).

The computing device 330 receives the signal transmitted from the phasesensitive amplifier 329, the computing device 330 transmits the controlsignal to the control circuit 300 connected to the computing device 330through the signal line. The control signal controls the oscillator 298from the received signal and the oscillation frequency which is swept bythe oscillator 298 and received from control circuit 300 such that theoscillation frequency of the oscillator 298, i.e., the sweep range ofthe modulation frequency includes the range of the change in resonancefrequency of the ultrasonic detector 328.

In an example of the sensitivity characteristics of the ultrasonicdetector shown in FIG. 21, for example, the computing device 330 maytransmit the signal for controlling the sweep of the oscillationfrequency of the oscillator 298 to the control circuit 300 such that themodulation frequencies of the first light source 301 and the secondlight source 302 are swept in the range broader than the frequency of ahalf-value width of the resonance characteristics. The computing device330 may also transmit the signal for controlling the sweep of theoscillation frequency of the oscillator 298 to the control circuit 300such that the modulation frequencies of the first light source 301 andthe second light source 302 are swept in the frequency range of afraction of the peak value of the resonance characteristics, e.g., ahalf of the peak value. The control circuit 300 controls the oscillationfrequency of the oscillator 298 according to the control signaltransmitted from the computing device 330.

As described above, in the blood constituent concentration measuringapparatus of the third embodiment, the light outputted from the firstlight source 301 and the light outputted from the second light source302 are intensity-modulated using the signals having the same frequency.Therefore, in the third embodiment, there is no influence of theunevenness of the frequency characteristics in the measuring system,which becomes troublesome in the conventional technique when theintensity modulation is performed using the signals having the pluralfrequencies.

As described above, in the blood constituent concentration measuringapparatus of the third embodiment, even if the resonance characteristicsof the ultrasonic detector 328 is changed, the modulation frequency ofthe light with which the living body is irradiated is swept to thephotoacoustic signal in the living body. Therefore, the value, which isdetected with high sensitivity in association with the resonancefrequency of the ultrasonic detector 328, is selected from the detectionvalues of the photoacoustic signal, and the value is integrated, whichallows the blood constituent concentration to be correctly measured.

A control method of blood constituent concentration measuring apparatusof the third embodiment is a control method of blood constituentconcentration measuring apparatus sequentially including a lightgenerating procedure in which light generating means generates two lightbeams having different wavelengths; a frequency sweep procedure in whichthe frequency sweep means sweeps a frequency, the light generated in thelight generating procedure being modulated in the frequency; a lightmodulation procedure in which light modulation means electricallyintensity-modulates each of the two light beams having the mutuallydifferent wavelengths using signals having the reverse phases, where thesignals are swept in the frequency sweep procedure; a light outgoingprocedure in which light outgoing means multiplexes into one light fluxto output the two intensity-modulated light beams having the mutuallydifferent wavelengths toward the living body, which areintensity-modulated in the light modulation procedure; an acoustic wavedetection procedure in which acoustic wave detection means detects anacoustic wave i.e., a photoacoustic signal generated in the living bodyby the light outputted in the light outgoing procedure; and anintegration procedure in which integration means integrates the acousticwave in a swept modulation frequency range, the acoustic wave beingdetected in the acoustic wave detection procedure.

In the control method of blood constituent concentration measuringapparatus of the third embodiment, the control circuit 300 shown in FIG.22 controls the frequency, the output of the oscillator 298 which isswept in the oscillation frequency is transmitted to the drive circuit297 through the drive circuit 303 and 180°-phase shifter 299respectively, the drive circuit 303 and drive circuit 297 which receivethe swept frequency drive the first light source 301 and the secondlight source 302 to cause to emit the light beams respectively, and thelight beams are intensity-modulated. In this case, the first lightsource 301 and the second light source 302 emit the light beamsrespectively, and the emitted light beams can be intensity-modulated bythe swept frequency.

The wavelengths of the first light source 301 and the second lightsource 302 are set at the two light wavelengths in which the differencein absorption exhibited by the blood constituents set as the measuringobject is larger than the difference in absorption exhibited by thewater. Alternatively, the difference in absorption exhibited by thewater may be set to zero, and one of the light wavelengths may be set atthe wavelength in which the blood constituent set as the measuringobject exhibits the characteristic absorption, and the other lightwavelength may be set at the wavelength in which the water exhibits theabsorption similar to that in one of the light wavelengths. It isdesirable that the wavelengths of the first light source 301 and thesecond light source 302 are set at the wavelengths in which thedifference in absorption exhibited by the blood constituents set as themeasuring object is larger than the difference in absorption exhibitedby other blood constituents except for the blood constituents set as themeasuring object. Setting the wavelengths of the first light source 301and the second light source 302 at the above values can also be appliedin the first embodiment, the second embodiment, and the later-mentionedfourth embodiment, fifth embodiment, and sixth embodiment in addition tothe third embodiment.

The light beam outputted from the first light source 301 and the lightbeam outputted from the second light source 302 are inputted to thecoupler 308, and the light beams are multiplexed into one light flux.Then, the predetermined position of the living body test region 309 isirradiated with the light flux, and thereby the acoustic wave, i.e., thephotoacoustic signal is generated in the living body test region 309.

As described above, the living body is irradiated with theintensity-modulated light beam, and the photoacoustic signal generatedin the living body by the intensity-modulated light is detected by theultrasonic detector 328 through the acoustic coupler 327 shown in FIG.22, and the photoacoustic signal is converted into the electric signalproportional to the magnitude of the photoacoustic signal. Then, thephase sensitive amplifier 329 performs the synchronous detection, theamplification, and the filtering to the electric signal, the electricsignals are integrated and averaged for the predetermined time, and theelectric signal is transmitted to the computing device 330.

As described above, the detected photoacoustic signal is integrated asthe electric signal proportional to the pressure in the frequency rangewhich is swept by the computing device 330 shown in FIG. 22, thedetection value or frequency in the resonance frequency in which thedetection sensitivity is increased is selected in the electric signalsproportional to the magnitude of the integrated photoacoustic signal,the integration is performed in the selected range, and the bloodconstituent concentration is computed.

According to the above method, even if the resonance frequency of theultrasonic detector 328, which detects the photoacoustic signal in theliving body, is changed, the detection values of the photoacousticsignals can be selected and integrated in the frequency corresponding tothe resonance frequency of the ultrasonic detector 328 to compute theblood constituent concentration. Therefore, the blood constituentconcentration can correctly be measured.

A blood constituent concentration measuring apparatus of the thirdembodiment is a blood constituent concentration measuring apparatus inwhich the acoustic wave detection means tracks the modulation frequencyto detect the acoustic wave, i.e., the photoacoustic signal generatedthe living body to be measured, the modulation frequency being swept bythe frequency sweep means, and the integration means integrates theacoustic wave in the modulation frequency range where the acoustic wavedetection means has high detection sensitivity, the photoacoustic signalbeing detected by the acoustic wave detection means.

The configuration of the blood constituent concentration measuringapparatus of the third embodiment is similar to that of the bloodconstituent concentration measuring apparatus described with referenceto FIGS. 20 and 22.

In the above blood constituent concentration measuring apparatusdescribed with reference to FIGS. 20 and 22, a blood constituentconcentration measuring apparatus of the third embodiment is the case,in which the magnitude of the photoacoustic signal detected by theultrasonic detector 127 or the ultrasonic detector 328 according to thesweep of the modulation frequency is tracked and monitored as the outputof the phase sensitive amplifier 128 or the phase sensitive amplifier329 by the computing device 129 or the computing device 330, themodulation frequency in which the sensitivity of the ultrasonic detector127 or the ultrasonic detector 328 is increased is searched, and themagnitude of the photoacoustic signal detected in the range of themodulation frequency in which the sensitivity of the ultrasonic detector127 or the ultrasonic detector 328 is increased is obtained andintegrated from the output of the phase sensitive amplifier 128 or thephase sensitive amplifier 329.

As described above, in the blood constituent concentration measuringapparatus of the third embodiment, the magnitude of the photoacousticsignal detected near the modulation frequency in which the sensitivityof the ultrasonic detector 127 and the ultrasonic detector 328 becomesthe maximum is obtained and integrated from the output of the phasesensitive amplifier 128 and phase sensitive amplifier 329, and the bloodconstituent concentration can correctly be measured.

A control method of blood constituent concentration measuring apparatusof the third embodiment is a constituent concentration measuringapparatus controlling method in which the acoustic wave detectionprocedure is a procedure in which the modulation frequency is tracked todetect the acoustic wave generated in the living body, the modulationfrequency being swept in the frequency sweep procedure, and theintegration procedure is a procedure in which the acoustic wave isintegrated in the modulation frequency range where detection sensitivityof the photoacoustic signal is high in the acoustic wave detectionprocedure, the acoustic wave being detected in the photoacoustic signaldetection procedure.

In the above control method of blood constituent concentration measuringapparatus, the control method of blood constituent concentrationmeasuring apparatus of the third embodiment is the case in which, in theacoustic wave detection procedure, for example, in the blood constituentconcentration measuring apparatus described with reference to FIGS. 20and 22, the ultrasonic detector 127 or the ultrasonic detector 328detects the acoustic wave according to the sweep of the modulationfrequency, in the integration procedure, the magnitude of thephotoacoustic signal detected by the ultrasonic detector 127 or theultrasonic detector 328 is tracked and monitored as the output of thephase sensitive amplifier 128 or the phase sensitive amplifier 329 tosearch the point of the modulation frequency in which the sensitivity ofthe ultrasonic detector 127 or the ultrasonic detector 328 is increasedby the computing device 129 or the computing device 330, and themagnitude of the photoacoustic signal detected in the modulationfrequency range where the ultrasonic detector 127 or the ultrasonicdetector 328 has the high detection sensitivity is obtained andintegrated from the output of the phase sensitive amplifier 128 or thephase sensitive amplifier 329.

As described above, in the control method of blood constituentconcentration measuring apparatus of the third embodiment, the acousticwave, i.e., the photoacoustic signal generated in the living body byirradiating the living body with the light signal in which the intensitymodulation frequency is swept, the modulation frequency corresponding tothe resonance frequency in which the sensitivity of the ultrasonicdetector is increased is searched from the detected value, and thephotoacoustic signal is detected near the modulation frequencycorresponding to the resonance frequency in which the sensitivity of theultrasonic detector becomes the maximum. Therefore, the control methodof blood constituent concentration measuring apparatus of correctlymeasuring the blood constituent can be provided.

A blood constituent concentration measuring apparatus of the thirdembodiment is a blood constituent concentration measuring apparatusfurther including blood constituent concentration computation means forcomputing the blood constituent concentration in the living body fromthe magnitude of the detected photoacoustic signal.

The configuration of the blood constituent concentration measuringapparatus of the third embodiment is the case in which, for example,similarly to the blood constituent concentration measuring apparatusdescribed with reference to FIGS. 20 and 22, the computing device 129 orthe computing device 330 has the function as the blood constituentconcentration computation means.

That is, the blood constituent concentration measuring apparatus of thethird embodiment is the case in which, in the blood constituentconcentration measuring apparatus shown in FIGS. 20 and 22, thecomputing device 129 or the computing device 330 has the function as theblood constituent concentration computation means for computing theblood constituent concentration according to the predeterminedcomputation method after the signal received from the phase sensitiveamplifier 128 or the phase sensitive amplifier 329 is integrated andaveraged.

As to the predetermined computation method, for example, numerical dataor a theoretical formula indicating the relationship between the bloodconstituent amount of the measuring object in the living body and themagnitude of the photoacoustic signal generated by irradiating theliving body with the light having the wavelength in which the bloodconstituent of the measuring object exhibits the absorption may be used.

As described above, in the blood constituent concentration measuringapparatus of the third embodiment, the blood constituent concentrationcan easily be measured by including the blood constituent concentrationcomputation means.

A control method of blood constituent concentration measuring apparatusof the third embodiment is a control method of blood constituentconcentration measuring apparatus further including a blood constituentconcentration computation procedure of computing the blood constituentconcentration in the living body from the magnitude of the photoacousticsignal detected in the acoustic wave detection procedure.

The control method of blood constituent concentration measuringapparatus of the third embodiment is the case where the acoustic wavedetection procedure of the control method of blood constituentconcentration measuring apparatus further comprises the bloodconstituent concentration computation procedure, in which the computingdevice 129 or the computing device 330 of the constituent concentrationmeasuring apparatus described with reference to FIGS. 20 and 22 computesthe blood constituent concentration according to the predeterminedcomputation method after the signal received from the phase sensitiveamplifier 128 or the phase sensitive amplifier 329 is integrated andaveraged.

As to the predetermined computation method, for example, numerical dataor the theoretical formula indicating the relationship between the bloodconstituent amount of the measuring object in the living body and themagnitude of the photoacoustic signal generated by irradiating theliving body with the light having the wavelength in which the bloodconstituent of the measuring object exhibits the absorption may be used.

As described above, in the control method of blood constituentconcentration measuring apparatus of the third embodiment, the bloodconstituent concentration can easily be measured by including the bloodconstituent concentration computation procedure.

A blood constituent concentration measuring apparatus of the thirdembodiment further includes recording means for recording thephotoacoustic signal detected by the acoustic wave detection meanscorresponding to the swept modulation frequency.

The configuration of the blood constituent concentration measuringapparatus of the third embodiment is the case in which, for example, inthe blood constituent concentration measuring apparatus described withreference to FIGS. 20 and 22, a recorder (not shown) which is of therecording means is connected to the computing device 129 or thecomputing device 330.

The recorder records the signal corresponding to the modulationfrequency. The computing device 129 or the computing device 330 receivesthe signal from the phase sensitive amplifier 128 or the phase sensitiveamplifier 329, and the signal is proportional to the magnitude of thephotoacoustic signal generated in the living body test region 110 or theliving body test region 309.

In the case where the resonance frequency is changed in the ultrasonicdetector 127 or the ultrasonic detector 328, the recording performed bythe recorder can determine whether or not the modulation frequency sweeprange of the light with which the living body test region 110 or theliving body test region 309 is irradiated includes the range where theresonance frequency is changed. The recording performed by the recordercan also determine whether or not the value accurately measured in themodulation frequency corresponding to the resonance frequency isselected from the values of the photoacoustic signals detected by theultrasonic detector 127 or the ultrasonic detector 328. In addition tothe third embodiment, the recording means can also be applied to thefirst embodiment, the second embodiment, and the later-mentioned fourthembodiment, fifth embodiment, and sixth embodiment.

As described above, in the blood constituent concentration measuringapparatus of the third embodiment, the blood constituent concentrationcan appropriately be measured by including the recording means.

A control method of blood constituent concentration measuring apparatusaccording to the third embodiment is a control method of bloodconstituent concentration measuring apparatus further including arecording procedure in which the photoacoustic signal detected by theacoustic wave detection procedure is recorded corresponding to the sweptmodulation frequency after the acoustic wave detection procedure.

The control method of blood constituent concentration measuringapparatus of the third embodiment is the case in which, for example, inthe control method of blood constituent concentration measuringapparatus described with reference to FIGS. 20 and 22 further includesthe recording procedure of recording the signal received by thecomputing device 129 or the computing device 330 from the phasesensitive amplifier 128 or the phase sensitive amplifier 329 in therecorder (not shown) connected to the computing device 129 or thecomputing device 330 corresponding to the swept oscillation frequencyafter the acoustic wave detection procedure of the control method ofblood constituent concentration measuring apparatus.

In the case where the resonance frequency is changed in the ultrasonicdetector 127 or the ultrasonic detector 328, the recording performed bythe recorder can determine whether or not the modulation frequency sweeprange of the light with which the living body test region 110 or theliving body test region 309 is irradiated includes the range where theresonance frequency is changed. The recording performed by the recordercan also determine whether or not the value accurately measured in themodulation frequency corresponding to the resonance frequency isselected from the values of the photoacoustic signals detected by theultrasonic detector 127 or the ultrasonic detector 328.

As described above, in the control method of blood constituentconcentration measuring apparatus of the third embodiment, the bloodconstituent concentration can appropriately be measured by including therecording procedure. In addition to the third, embodiment, the recordingprocedure can also be applied to the first embodiment, the secondembodiment, and the later-mentioned fourth embodiment, fifth embodiment,and sixth embodiment.

Fourth Embodiment

FIG. 23 is a schematic view showing an example of a blood constituentconcentration measuring apparatus according to a fourth embodiment. Theblood constituent concentration measuring apparatus shown in FIG. 23includes a light generation unit 11 which is of the light generatingmeans for generating the light, a light modulation unit 12 which is ofthe light modulation means for electrically intensity-modulating thelight generated by the light generation unit 11 at constant frequency, alight outgoing unit 13 which is of the light outgoing means foroutputting intensity modulated light 1 intensity-modulated by the lightmodulation unit 12 toward the living body test region 97 which is of thetest subject, and an ultrasonic detection unit 14 which is of theacoustic wave detection means for detecting an acoustic wave, i.e., aphotoacoustic signal 3 generated from the living body test region 97irradiated with the intensity modulated light 1. In the bloodconstituent concentration measuring apparatus, the living body testregion 97 and the acoustic matching substance which have thesubstantially same acoustic impedance as the living body test region 97can be arranged in an inside 22 located between the light outgoing unit13 and the ultrasonic detection unit 14.

The blood constituent concentration measuring apparatus shown in FIG. 23further includes a container 21, a sound absorbing material 15, atemperature measurement unit 16, and an outgoing window 17. In thecontainer 21, the inside 22 located between the light outgoing unit 13and the ultrasonic detection unit 14 is filled with the acousticmatching substance having the substantially equal acoustic impedance asthe living body test region 97. The sound absorbing material 15 isarranged in an inner wall surface of the container 21. The temperaturemeasurement unit 16 measures the temperature of the acoustic matchingsubstance arranged in the container 21. The outgoing window 17 istransparent for the intensity modulated light 1 arranged in the innerwall surface of the container 21. FIG. 23 shows the state in which theacoustic matching substance and the living body test region 97 arearranged in the inside 22 of the container 21. The light outgoing unit13 and the ultrasonic detection unit 14 are arranged across the livingbody test region 97 in the inside 22 filled with the acoustic matchingsubstance having the substantially equal acoustic impedance as theliving body test region 97, and the surfaces of the outgoing window 17and ultrasonic detection unit 14 are in contact with the acousticmatching substance respectively.

FIG. 23 shows an example in which the light outgoing unit 13 and theultrasonic detection unit 14 are arranged at positions substantiallyfacing each other. The photoacoustic signal 3 emitted from the livingbody test region 97 is detected with the largest signal intensity in thedirection in which the light outgoing unit 13 outputs the intensitymodulated light 1. The accuracy of the photoacoustic signal detected bythe ultrasonic detection unit 14 can further be improved by arrangingthe light outgoing unit 13 and the ultrasonic detection unit 14 whilesubstantially facing each other. In addition to the fourth embodiment,the arrangement in which the light outgoing unit 13 and the ultrasonicdetection unit 14 substantially face each other can also applied to thefirst embodiment, the second embodiment, the third embodiment, and thelater-mentioned, fifth embodiment and sixth embodiment.

The light generation unit 11 generates the light. For example, afluorescent lamp, a halogen lamp, laser including semiconductor laserlight generating devices including a light generating diode, and lightgenerating devices including a light generating diode can be cited as anexample of the light generation unit 11. It is preferable that the lightgeneration unit 11 emits the light having the wavelength absorbed by theconstituent whose concentration is measured. For example, the laser andlight generating device having the wavelength selectivity is preferablefor the light generation unit 11.

The light modulation unit 12 electrically intensity-modulates the lightgenerated by the light generation unit 11 at a constant frequency. Thelight modulation unit including the oscillator, the drive circuit, andthe 180°-phase shifter can be cited.

Preferably, the light generation unit 11 generates the two light beamshaving the wavelengths λ₁ and λ₂, and preferably the light modulationunit 12 intensity-modulates the light beams having the wavelengths λ₁and λ₂ into the intensity modulated light 1 having the same frequencyand reverse phases. For example, assuming that the glucose bloodconcentration is set at an index of the blood sugar level and water isused as the acoustic matching substance, because glucose exhibits theabsorption at 1600 nm, the wavelength near 1600 nm may be selected asthe wavelength λ₁ and the wavelength near 1400 nm in which theabsorption coefficients of water are equal to each other may be selectedas the wavelength λ₂.

The concentration measured in the case where the wavelength absorbed bythe blood constituent is selected as the wavelength λ₁ and thewavelength in which the absorption coefficients of water are equal tothose in the wavelength λ₁ is selected as the wavelength λ₂ will bedescribed below. When the absorption coefficients α₁ ^((b)), α₂ ^((b))to which the background water mainly contributes and the molarabsorption coefficients α₁ ⁽⁰⁾, α₂ ⁽⁰⁾ of the blood constituent areknown for the wavelengths λ₁ and λ₂, the concentration M is determinedby solving the formula (1) which is of the simultaneous equationsincluding the photoacoustic signal measured value s₁ and s₂ in thewavelengths. Where C is a variable coefficient which is hardlycontrolled or calculated, i.e., C is an unknown multiplier depending onthe acoustic coupling, the ultrasonic detector sensitivity, the distancer between the irradiation portion and the living body test region, thespecific heat, the thermal expansion coefficient, the sound velocity,the modulation frequency, and the absorption coefficient. When C isdeleted in the formula (1), the formula (4) is obtained, and theconcentration M can be determined from the photoacoustic signal s₁, s₂and the already known absorption coefficient. However, in the formula(4), it is assumed that the absorption coefficient α₁ ^((b)), α₂ ^((b))to which the background water mainly contributes are substantially equalto each other for the wavelengths λ₁ and λ₂. The formula (4) also hasthe feature of s₁≅s₂. Thus, the influence of the water on thephotoacoustic signal can be removed by utilizing the two intensitymodulated light beams having the mutually different wavelengths in whichthe frequencies are equal to each other and the phases are reversed toeach other for the intensity modulated light 1.

The light outgoing unit 13 outputs the intensity modulated light 1 whichis intensity-modulated by the light modulation unit 12. The lightoutgoing unit 13 is a member arranged in the portion where the intensitymodulated light 1 is outputted, and preferably the light outgoing unit13 is made of the material transparent to the intensity modulated light1. Glass and plastic can be cited as an example of the transparentmaterial. In the case where the light outgoing unit 13 is in contactwith the acoustic matching substance, preferable the light outgoing unit13 is made of the material which does not react with the acousticmatching substance. A quartz plate, an optical glass plate, and asapphire plate can be cited. The light outgoing unit 13 may include anoptical fiber which can guide the intensity modulated light 1. The lightgeneration unit 11 and the light modulation unit 12 are arranged atpositions distant from the light outgoing unit 13 by including theoptical fiber, which allows the intensity modulated light 1 to be guidedto the position where the living body test region 97 is irradiated.

The ultrasonic detection unit 14 detects the photoacoustic signal 3which is of the acoustic wave. Examples of the ultrasonic detection unitinclude the ultrasonic detection unit such as a crystal microphone, aceramic microphone, and a ceramic ultrasonic wave sensor in which themagneto-striction effect or electro-striction effect is utilized, theultrasonic detection unit such as a moving-coil microphone and a ribbonmicrophone in which electromagnetic induction is utilized, the acousticwave detector such as a capacitor microphone in which electrostaticeffect is utilized, and the ultrasonic detection unit such as amagneto-striction vibrator in which magneto-striction is utilized. Theultrasonic detection unit including crystal such as PZT and PVDF can becited as an example of the ultrasonic detection unit in whichpiezoelectric effect is utilized. An underwater microphone such as ahydrophone is preferably used because the acoustic wave propagatingthrough the acoustic matching substance is detected. Preferably, a layer(for example, silicone rubber) for performing the matching with theacoustic impedance of the acoustic matching substance is formed in thesurface of the ultrasonic detection unit.

The temperature measurement unit 16 is a thermometer which measures thetemperature of the acoustic matching substance. The acoustic matchingsubstance is preferably in a liquid, sol, or gel, so that a contact typethermometer can be used as the temperature measurement unit 16. Anon-contact type radiation thermometer may be used.

The blood constituent concentration measuring apparatus shown in FIG. 23may further include a thermostat unit (not shown) which adjusts thetemperature of the acoustic matching substance according to thetemperature measured by the temperature measurement unit 16. A heatercan be cited as an example of the thermostat unit. The temperatures ofthe acoustic matching substance and photoacoustic signal surface can bestabilized by adjusting the temperature of the acoustic matchingsubstance according to the temperature measured by the temperaturemeasurement unit 16. For example, the temperature of the acousticmatching substance can be adjusted according to the temperature rise.The stabilization of the temperatures of acoustic matching substance andphotoacoustic signal surface stabilizes the change in photoacousticsignal 3 caused by the temperature change, so that the computationaccuracy of the blood constituent concentration is increased.

In the container 21 shown in FIG. 23, the inside 22 can be filled withthe acoustic matching substance.

FIG. 23 shows the example in which the sound absorbing material 15 isincluded in the inner wall surface of the container 21. The soundabsorbing material 15 absorbs the photoacoustic signal 3. For example,the sound absorbing material 15 can be made of the material in whichmetal oxide powders (titanium oxide or tungsten oxide) are included inan epoxy resin. The multiple-reflection acoustic wave generated from theunevenness of the internal structure of the living body test region 97can be absorbed and removed by including the sound absorbing material 15in at least one part of the inner wall surface of the container 21.Therefore, the ultrasonic detection unit 14 can efficiently detect thephotoacoustic signal 3 emitted from the living body test region 97.

FIG. 23 also shows the example in which the container 21 includes theoutgoing window 17. The outgoing window 17 is transparent to theintensity modulated light 1. The transparent glass and plastic can becited as an example of the outgoing window 17. Preferably, the outgoingwindow 17 is scratch resistant, and the quartz plate, the optical glassplate, and the sapphire plate can be cited as an example of the outgoingwindow 17. Preferably, the outgoing window 17 is made of the materialwhich does not absorb the intensity modulated light 1. The lightoutgoing unit 13 can be arranged outside the inside 22 of the container21 by including the outgoing window 17, so that the light outgoing unit13 can easily be arranged. Because the intensity modulated light 1 canbe outputted from the inner wall surface of the container 21, theirregularity is eliminated in the inner wall surface of the container21, and the reflection of the photoacoustic signal 3 can be decreased.

The acoustic matching substance has the substantially same acousticimpedance as the living body test region 97. Examples of the acousticmatching substance include rubber, a soft solid such as resin, a liquid,and sol or gel. The water may be used as the acoustic matchingsubstance. That is, the container 21 may be filled with the water whichis of the acoustic matching substance. Because the acoustic impedance ofthe living body is close to the water, when the photoacoustic signal 3is detected under the environment in which the inside 22 which is of thesurroundings of the living body test region 97 is surrounded by thewater, the degradation of the photoacoustic signal 3 can be decreased.The degradation of the photoacoustic signal 3 is caused by the boundaryreflection between the living body test region 97 and the inside 22which is of the surroundings thereof and by the contact between theliving body test region 97 and the ultrasonic detection unit 14.

FIG. 24 is a transverse sectional view taken on line D-D′ of FIG. 23,and FIG. 24 shows a first mode of the blood constituent concentrationmeasuring apparatus. In the container 21, the shape in transversesection is formed in the circle. The light outgoing unit 13 and theultrasonic detection unit 14 are arranged in the side face of thecontainer 21 while substantially facing each other.

FIG. 25 is a transverse sectional view taken on line D-D′ of FIG. 23,and FIG. 25 shows a second mode of the blood constituent concentrationmeasuring apparatus. In the container 21 shown in FIG. 25, the shape intransverse section is formed in the semi-circle, and the light outgoingunit 13 is arranged at the position of the substantial center point ofthe semi-circle. FIG. 25 also shows the example in which ultrasonicdetection units 14 a, 14 b, 14 c, 14 d, and 14 e are arranged in the arcportion of the semi-circle of the container 21. The ultrasonic detectionunit 14 a is arranged at the position where the ultrasonic detectionunit 14 a faces the light outgoing unit 13, and the ultrasonic detectionunits 14 b to 14 e are arranged in the arc portion in the dispersedmanner.

As shown in FIG. 25, the shape in transverse section of the container 21is formed in the semi-circle, and the light outgoing unit 13 is arrangedin the substantial center point of the circle. Therefore, the distancebetween the side face of the case corresponding to the arc portion ofthe semi-circle and the light outgoing unit 13 can be uniformed.Accordingly, when the living body test region 97 is placed so as to bepressed against the flat surface including the center of thesemi-circle, the photoacoustic signal 3 is generated in the substantialcenter of the semi-circle, and the photoacoustic signal 3 spreadsradially. At this point, the distance between the ultrasonic detectionunits 14 a to 14 e and the generation source of the photoacoustic signal3 is kept constant, so that the ultrasonic detection units 14 a to 14 ecan detect the same-phase photoacoustic signals 3. When thephotoacoustic signals 3 detected by the ultrasonic detection units 14 ato 14 e are multiplexed, the photoacoustic signal 3 can efficiently bedetected. When the detection signals are compared to each other at thesame time, the influence caused by the structure inside the living bodytest region 97 can also be corrected. Thus, the accuracy of thephotoacoustic signal can further be increased by improving the soundcollective state in the acoustic wave detection means. The acoustic wavedetection means can more efficiently detect the radially spreadphotoacoustic signal by arranging two acoustic wave detection means inthe side face of the case corresponding to the arc portion of thesemi-circle.

FIG. 26 is a longitudinal sectional showing a fourth mode of the bloodconstituent concentration measuring apparatus. In the blood constituentconcentration measuring apparatus shown in FIG. 26, the bottom surfaceinside the container 21 is formed in a hemisphere. The blood constituentconcentration measuring apparatus of the fourth mode can be used in thecase where the section E-E′ is the transverse section shown in FIG. 25.In FIG. 26, an ultrasonic detection unit 14 f is shown in the bottomsurface, and the ultrasonic detection unit 14 f is arranged at theposition where the distance from the light outgoing unit 13 issubstantially equal to the distance between the light outgoing unit 13and the ultrasonic detection unit 14 a. Thus, the photoacoustic signal 3spreading radially from the living body test region 97 can be detectedmore efficiently by utilizing the ultrasonic detection unit 14 f inaddition to the ultrasonic detection units 14 a to 14 e shown in FIG.25. The section E-E′ is not limited to FIG. 25. For example, the shapein transverse section may be formed in a sector having arbitrary anglessuch as 45 degrees, 90 degrees, and 135 degrees.

A fifth mode of the blood constituent concentration measuring apparatuswill be described with reference to FIGS. 27 and 28. FIG. 27 is alongitudinal sectional showing the fifth mode of the blood constituentconcentration measuring apparatus. FIG. 28 is a transverse sectionalview taken on line F-F′ of FIG. 27. In the blood constituentconcentration measuring apparatus shown in FIGS. 27 and 28, thecontainer 21 is formed in the elliptic hemisphere including two focalpoints in section, and the light outgoing unit 13 and the ultrasonicdetection unit 14 are arranged at the two focal points respectively. Thecontainer 21 is formed in the elliptic hemisphere including the twofocal points in section, and the light outgoing unit 13 and theultrasonic detection unit 14 are arranged near the two focal pointsrespectively. Therefore, the photoacoustic signal 3 can be scattered atthe bottom portion of the case and efficiently collected by theultrasonic detection unit 14. Because the distance in which thephotoacoustic signal 3 reaches the ultrasonic detection unit 14 is notchanged, the photoacoustic signal 3 is hardly affected by the influenceof the multiple-scattering acoustic wave. Thus, the accuracy of thephotoacoustic signal 3 can further be increased by improving the soundcollective state in the acoustic wave detection means. As shown in FIG.27, the container 21 includes the reflection material 18 in the innerwall surface of the bottom portion. The reflection material 18 reflectsthe photoacoustic signal 3. Preferably, the reflection material 18 doesnot react with the water. For example, when the water is used as theacoustic matching substance, the stable metal such as stainless steeland aluminum can be cited. The efficiency of collecting thephotoacoustic signal 3 with acoustic wave detection means can beimproved by including the reflection material 18 in at least one part ofthe inner wall surface of the container 21. Therefore, the accuracy ofthe photoacoustic signal 3 detected by the ultrasonic detection unit 14can be further increased.

Although the bottom surface is described in the fifth mode of the bloodconstituent concentration measuring apparatus, as shown in FIG. 28, thecontainer 21 may be formed in the ellipse in transverse section, and thelight outgoing unit 13 and the ultrasonic detection unit 14 may bearranged at the substantial focal points of the ellipse respectively.The shape of the inner wall surface is formed in the ellipse intransverse section, and the light outgoing unit 13 and the ultrasonicdetection unit 14 are arranged at the substantial focal points of theellipse respectively. Therefore, the photoacoustic signal 3 can bescattered by the side face of the inner wall surface of the container 21and efficiently collected by the ultrasonic detection unit 14. Thus, theaccuracy of the photoacoustic signal 3 can further be increased byimproving the sound collective state in the ultrasonic detection unit14.

As described above, by including the container 21, the living body testregion 97 is arranged in the inside 22 of the container 21 filled withthe acoustic matching substance having the substantially equal acousticimpedance as the living body test region 97, and the photoacousticsignal 3 can be detected from the living body test region 97 under theenvironment in which the inside 22 which is of the surroundings of theliving body test region 97 is surrounded by the acoustic matchingsubstance. The photoacoustic signal 3 is detected under the environmentin which the inside 22 which is of the surroundings of the living bodytest region 97 is surrounded by the acoustic matching substance, whichallows the degradation of the photoacoustic signal 3 to be decreased.The degradation of the photoacoustic signal 3 is caused by the boundaryreflection between the living body test region 97 and the inside 22which is of the surroundings thereof and by the contact between theliving body test region 97 and the ultrasonic detection unit 14.

The living body test region 97 is a human living body. Although thefinger is shown in FIGS. 23 to 28 by way of example, any part of theliving body may be used as the living body test region 97. For example,a hand and an arm may be used as the living body test region 97.

An animal, a bird, and plants such as fruit and vegetable may be used asthe living body test region 97 which is of the object to be measured.The object to be measured includes a pipe through which a liquid flowsand the container such as a bottle and a tank in which the liquid sol orgel is reserved. For example, when the object to be measured is thefruit, the sugar of the fruit can be measured in the noninvasive manner.

As described above, the control method of blood constituentconcentration measuring apparatus according to the fourth embodimentincluding the light generating procedure in which the light generatingmeans generates the light; the light modulation procedure forelectrically intensity-modulating the light generated from the lightgenerating procedure at a constant frequency; the light outgoingprocedure in which the light modulation means outputs the intensitymodulated light 1 intensity-modulated in the light modulation proceduretoward the living body test region 97; and the acoustic wave detectionprocedure in which the acoustic wave detection means detects theacoustic wave, i.e., the photoacoustic signal 3 emitted from the livingbody test region 97 irradiated with the intensity modulated light 1 inthe light outgoing procedure. The control method of blood constituentconcentration measuring apparatus is characterized in that the lightoutgoing procedure and the acoustic wave detection procedure areperformed in the container 21 filled with the acoustic matchingsubstance having the substantially equal acoustic impedance as theliving body test region 97.

Thus, the living body test region 97 and the acoustic matching substancehaving the substantially equal acoustic impedance as the living bodytest region 97 can be arranged between the light outgoing unit 13 andthe ultrasonic detection unit 14, so that the acoustic matchingsubstance can be placed between the living body test region 97 and theultrasonic detection unit 14 to reduce the boundary reflection at theinterface between the living body test region 97 and the inside 22 whichis of the surroundings thereof.

Preferably, in the light outgoing procedure, as described above, thelight generation unit 11 generates the two light beams having themutually different wavelengths λ₁ and λ₂ and, in the light modulationprocedure, the light modulation unit 12 intensity-modulates these lightbeams having the different wavelengths λ₁ and λ₂ into the intensitymodulated lights 1 having the same frequency and reverse phases.

As shown in FIGS. 23 to 28, preferably, in the light outgoing procedure,the living body test region 97 is arranged while being contact with theoutgoing surface of the intensity modulated light 1 and the living bodytest region 97 is directly irradiated with the intensity modulated light1. The outgoing window 17 acts as the outgoing surface in FIGS. 23 to28. The light outgoing unit 13 acts as the outgoing surface, when theoutgoing window 17 is not included. The living body test region 97 isarranged so as to come into contact with the outgoing surface of theintensity modulated light 1, and the living body test region 97 isdirectly irradiated with the intensity modulated light 1. Therefore, thedegradation of the intensity modulated light 1 caused by the absorptionin the acoustic matching substance can be prevented. Accordingly,because the living body test region 97 is efficiently irradiated withthe intensity modulated light 1, the intensity is increased in thephotoacoustic signal 3 emitted from the living body test region 97, andthe accuracy of the photoacoustic signal 3 detected by the ultrasonicdetection unit 14 can further be increased. The arrangement in which theliving body test region 97 is in contact with the intensity modulatedlight 1 can also be applied in the first embodiment, the secondembodiment, third embodiment, and the later-mentioned fifth embodimentand sixth embodiment in addition to the fourth embodiment.

As shown in FIGS. 23 to 28, preferably, in the acoustic wave detectionprocedure, the photoacoustic signal 3 is detected through the acousticmatching substance having the substantially equal acoustic impedance asthe living body test region 97. FIGS. 23 to 28 show the example in whichthe detection is performed through the acoustic matching substance withwhich the inside 22 of the container 21 is filled. However, asolid-state substance such as silicone rubber arranged between theliving body test region 97 and the ultrasonic detection unit 14 may beused. The photoacoustic signal 3 is detected through the acousticmatching substance having the substantially equal acoustic impedance asthe living body test region 97, so that the boundary reflection betweenthe living body test region 97 and the inside 22 which is of thesurroundings thereof and the pressure and vibration applied to theultrasonic detection unit 14 can be prevented.

As shown in FIGS. 23 to 28, preferably, in the light outgoing procedure,the intensity modulated light 1 is arranged in the inner wall surface ofthe container 21 and the living body test region 97 is irradiated withthe intensity modulated light 1 through the outgoing window 17 which istransparent to the intensity modulated light 1. The container 21includes the outgoing window 17 which is transparent to the intensitymodulated light 1, which allows the light outgoing unit 13 to bearranged outside the container 21. Therefore, the light outgoing unit 13is easily arranged. Because the intensity modulated light 1 can beoutputted from the inner wall surface of the container 21, theirregularity is eliminated in the inner wall surface of the container21, and the reflection of the photoacoustic signal 3 can be decreased.

As shown in FIGS. 23 to 28, in the living body test region 97,preferably the region irradiated with the intensity modulated light 1 iscovered with the liquid, sol, or gel acoustic matching substance. In theliving body test region 97, the region irradiated with the intensitymodulated light 1 is covered with the liquid, sol, or gel acousticmatching substance, so that the photoacoustic signal 3 can be detectedfrom the living body test region 97 under the environment in which theinside 22 which is of the surroundings of the living body test region 97is surrounded by the acoustic matching substance.

EXAMPLES

Specific examples in the fourth embodiment will be described below.

First Example

A first example in which the light generating means generates the twolight beams having the different wavelengths and the light modulationmeans intensity-modulates the two light beams into the intensitymodulated light beams having the same frequency and reverse phases willbe described below with reference FIG. 29. FIG. 29 is a circuit diagramshowing an example of the blood constituent concentration measuringapparatus. An oscillator 51 drives drive circuits 53 a and 53 b at aconstant frequency. A 180°-phase shifter 52 is arranged between theoscillator 51 and the drive circuit 53 b, and the drive circuit 53 b isdriven in the phase reversed to the phase of the drive circuit 53 a.Light generation units 11 a and 11 b generate the light beams having thedifferent wavelengths. The drive circuit 53 a intensity-modulates thelight generated by the light generation unit 11 a, and the drive circuit53 a outputs the intensity modulated light 1 a. The drive circuit 53 bintensity-modulates the light generated by the light generation unit 11b, and the drive circuit 53 b outputs the intensity modulated light 1 b.Therefore, the intensity modulated light beams 1 a and 1 b having thedifferent wavelengths in which the frequencies are equal to each otherwhile the phases reversed to each other can be generated. In the firstexample, the oscillator 51, the drive circuits 53 a and 53 b, and the180°-phase shifter 52 correspond to the light modulation unit 12 shownin FIG. 23.

A coupler 55 multiplexes the intensity modulated light beams 1 a and 1b, and the light outgoing unit 13 outputs the multiplexed light as theintensity modulated light 1. The living body test region 97 isirradiated with the intensity modulated light 1 outputted from the lightoutgoing unit 13, and the photoacoustic signal 3 emitted from the livingbody test region 97 is detected by the ultrasonic detection unit 14. Inthe photoacoustic signal 3 detected by the ultrasonic detection unit 14,the photoacoustic signal 3 is extracted by the filter 57, and thephotoacoustic signal 3 is outputted from the photoacoustic signal outputterminal 59 after the photoacoustic signal output terminal 59 isamplified by the phase sensitive amplifier 58.

Second Example

A second example of the blood constituent concentration measuringapparatus of the fourth mode shown in FIGS. 25 and 26 will be describedwith reference to FIGS. 30 and 31. FIG. 30 is a longitudinal sectionalview of the blood constituent concentration measuring apparatus, andFIG. 30 shows an example in which the blood constituent concentrationmeasuring apparatus is applied to a fingertip of the human body. FIG. 31is a transverse sectional view taken on line H-H′. Referring to FIGS. 30and 31, the inside 22 of the cylindrical container 21 into which theliving body test region 97 is inserted is filled with water, theoutgoing window 17 and the ultrasonic detection unit 14 are embedded inthe inner wall of the container 21. A power supply 31 which supplies theelectric power to a light source chip 39 b and the ultrasonic detectionunit 14, a phase sensitive amplifier 32 which amplifies the outputsignal of the ultrasonic detection unit 14, a signal processor 33 whichcomputes the blood constituent concentration, and a display processingunit 34 which display data on a display device (not shown) placedoutside the base are provided in the base of the container. Theultrasonic detection unit 14 and the signal processor 33 are connectedto each other with a connection cable 35. A temperature regulating unit36 is placed in the inner wall of the container 21, a heater 37 and atemperature measurement unit 16 are incorporated into the container 21so as to come into contact with the inside 22 of the container 21.

The bottom portion of the cylindrical container 21 is formed in aquarter sphere having a radius of 5 cm. In the ultrasonic detection unit14 incorporated into the container 21, a preamplifier 38 which amplifiesthe photoacoustic signal 3 detected by the ultrasonic detection unit 14are placed. The crystal such as PZT and PVDF having the piezoelectriceffect is used as the ultrasonic detection unit 14. A matching layer isformed in the surface of the ultrasonic detector unit 14 to match theacoustic impedance with the water. When silicone rubber which isfrequently used in a percutaneous treatment tool is used as the matchinglayer of the ultrasonic detection unit 14, the reflection can bedecreased by 9% in the surface.

In the inner wall of the container 21 filled with the water, the innerwall of the container 21 except for the surface of the ultrasonicdetection unit 14 is filled with a sound absorbing material 15 in orderto decrease the reflection at the interface between the materials of thematching layer and container 21. The material in which metal oxidepowders (titanium oxide or tungsten oxide) are included in the epoxyresin is effectively used as the sound absorbing material which preventsthe reflection. In the light outgoing unit 13 shown in FIG. 23, the twolight beams having the mutually different wavelengths are generated withlight source chips 39 a and 39 b and lenses 40 a and 40 b, the two lightbeams having the mutually different wavelengths are multiplexed with apolarization beam splitter 41, and the fingertip portion is irradiatedwith the collimate light through the outgoing window 17. Thesemiconductor laser is effectively used as the light source chips 39 aand 39 b from the viewpoints of price, size, and chip lifetime. As tothe two wavelengths, the wavelength of the light source chip 39 a is setat 1380 nm and the wavelength of the light source chip 39 b is set at1608 nm.

The intensity modulated light beams 1 a and 1 b from the light sourcechips 39 a and 39 b are collimated with the lenses 40 a and 40 b toadjust the distance between the light source chip 39 a and the lens 40a, the material and curvature of the lens 40 a, the distance between thelight source chip 39 b and the lens 40 b, and the material and curvatureof the lens 40 b, which allows the intensity modulated light beams 1 aand 1 b to be adjusted in the beam diameter suitable to thephotoacoustic measurement. In the second example, the two beam diametersare set at 5.0 mm. The scratch-resistant material in which theabsorption is not exhibited in the two wavelengths is suitable to theoutgoing window 17. For example, the quartz plate, the optical glassplate, and the sapphire plate can be used. A pressure sensitive devicein which the piezoelectric material is used is embedded in an edgeportion of the outgoing window 17 which is in contact with the livingbody test region 97, and the pressure sensitive device senses thepressure applied to the outgoing window 17 to start the supply of theelectric power to the light source chips 39 a and 39 b.

In the temperature regulating unit 36, the heater 37 is embedded in theinner wall of the container 21, the current to the heater 37 is adjustedwhile the difference between the temperature measured by the temperaturemeasurement unit 16 and the temperature setting value of the acousticmatching substance in the inside 22 of the container 21 is monitored.The temperature of the acoustic matching substance is set at 36° C.which is close to the body temperature of the living body. The metallayer (not shown) made of metal (copper or aluminum) having the highheat conductivity is provided in the inner wall of the container 21, thetemperature of the acoustic matching substance can efficiently becontrolled by bringing the heater 37 and the metal layer into contactwith each other.

Third Example

An example of the blood constituent concentration measuring apparatus ofthe fifth mode shown in FIGS. 27 and 28 will be described with referenceto FIGS. 32 and 33. FIG. 32 is a longitudinal sectional view of theblood constituent concentration measuring apparatus, and FIG. 32 showsan example in which the blood constituent concentration measuringapparatus is applied to the finger of the human body. FIG. 33 is atransverse sectional view taken on line N-N′ of FIG. 32. The bottomportion of the cylindrical container is formed in elliptic hemispherehaving a major axis of 100 mm and a minor axis of 50 mm. The intensitymodulated light beams 1 a and 1 b from the light source chips 39 a and39 b are guided to an optical fiber 42 through the lenses 40 a and 40 band the beam splitter 41. The intensity modulated light 1 incident tothe optical fiber 42 is guided to the outgoing window 17 through theoptical fiber 42, and the intensity modulated light 1 is outputted tothe inside 22 of the container 21. The living body test region 97 isirradiated with the intensity modulated light 1 outputted from theoutgoing window 17.

The lens 40 a or 40 b is placed at the end face of the optical fiber 42,the irradiation beam diameters of the intensity modulated light beams 1a and 1 b are adjusted from the distance between the lenses 40 a and 40b, and the beam diameters of the two intensity modulated light beams 1are set at 5.0 mm. The drive currents of the light source chips 39 a and39 b are adjusted such that the power of the irradiation intensitymodulated light 1 becomes 4 mW, and the intensity modulation isperformed at 200 kHz by the oscillator (not shown). The outgoing window17 is placed such that the interface between the outgoing window 17 andthe water which is of the acoustic matching substance becomes the focalpoint of the ellipse, namely, the interface between the outgoing window17 and the living body test region 97 is placed at the focal point ofthe ellipse during the measurement. A commercially available hydrophonein which the acoustic matching is performed with the water is used asthe ultrasonic detection unit 14, and the ultrasonic detection unit 14is placed at the focal point of the ellipse different from theirradiation portion of the living body test region 97. The needlehydrophone is adopted as the ultrasonic detection unit 14 to finelyadjust the position, and the ultrasonic detection unit 14 is placed atthe position where the photoacoustic signal becomes the maximum.

The outgoing window 17, the inner wall surface on a horizontal plane,and the bottom surface except for the outgoing window 17 are filled withthe reflection material 18 in order to efficiently reflect thephotoacoustic signal 3. The stable metal (stainless steel or aluminum),which does not chemically react with the water, is used as thereflection material 18. Other inner surfaces except for above portionsare filled with sound absorbing material 15 to decrease the influencemultiple reflections.

Fifth Embodiment

FIG. 34 is a circuit diagram of a blood constituent concentrationmeasuring apparatus according to a fifth embodiment. The bloodconstituent concentration measuring apparatus shown in FIG. 34 includeslight generating means for generating the intensity modulated light 1intensity-modulated at a constant frequency; a excitation light source23 which is of the light modulation means and light outgoing means; anacoustic wave generator 24 which outputs the acoustic wave 2; and anacoustic wave detector 25 which is of the acoustic wave detection meansfor detecting the acoustic wave, i.e., photoacoustic signal 3 and theacoustic wave 2, the photoacoustic signal 3 being emitted from theliving body test region 97 which is of the test subject irradiated withthe intensity modulated light 1, the acoustic wave 2 being transmittedthrough the living body test region 97 from the acoustic wave generator24. In FIG. 34, the circuit diagram of a blood constituent concentrationmeasuring apparatus according to the fifth embodiment further includes acontrol unit 26 which compares the signal intensity of the acoustic wave2 from the output signal 4 of the acoustic wave 2 detected by theacoustic wave detector 25, the control unit 26 outputting the controlsignal 5 to control a drive unit 27 such that the intensity of theacoustic wave 2 becomes a particular value; the drive unit 27 whichvaries the positions of the excitation light source 23, acoustic wavegenerator 24, and acoustic wave detector 25 by the control signal 5; andacoustic coupling elements 28 which are located in surfaces whereacoustic wave generator 24 and acoustic wave detector 25 come intocontact with the living body test region 97, the acoustic couplingelement 28 having the substantially equal acoustic impedance as theliving body test region 97.

FIG. 34 shows the example in which the blood constituent concentrationmeasuring apparatus has a transmission window 29 in a central portion ofthe acoustic wave generator 24 and the transmission window 29 transmitsthe intensity modulated light 1 from the excitation light source 23.Preferably, the acoustic wave generator 24 is arranged close to the beamof the intensity modulated light 1 from the excitation light source 23.The reflection/scattering can correctly be examined in the propagationpath of the photoacoustic signal 3 by arranging the acoustic wavegenerator 24 close to the beam of the intensity modulated light 1 fromthe excitation light source 23. Preferably, the acoustic wave 2 isgenerated to the living body test region 97 at the position close to theliving body test region 97. Because the photoacoustic signal 3 isgenerated near the cuticle of the living body test region 97 to whichthe intensity modulated light i is incident, the reflection/scatteringcan further correctly be examined in the propagation path of thephotoacoustic signal 3. The acoustic wave 2 can be causes to propagateefficiently to the living body test region 97 by generating the acousticwave 2 at the position near the living body test region 97.

The excitation light source 23 shown in FIG. 34 outputs the intensitymodulated light 1 which is intensity-modulated at the constantfrequency. The excitation light source 23 outputs the light having theabsorption wavelength of the measuring object whose concentration ismeasured. For example, in the case where the measuring object isglucose, the wavelength becomes 1608 nm. The light emitted at aparticular frequency from the light source device may beintensity-modulated at a constant frequency using the oscillator, thedrive circuit, the 180°-phase shifter, and the like. Examples of thelight source device, which emits the light at a particular frequency,include various lasers such as a gas laser, a solid-state laser, and thesemiconductor laser and the light generating diode. The bloodconstituent concentration measuring apparatus may further include alight shielding hood, around at least one part of the optical path ofthe intensity modulated light 1, the light shielding hood preventing theleakage of the intensity modulated light 1 outside the blood constituentconcentration measuring apparatus. The leakage of the intensitymodulated light 1 outside the blood constituent concentration measuringapparatus including portions of the living body test region 97 exceptfor the portion to be examined is prevented by further including thelight shielding hood. In addition to the fifth embodiment, the lightshielding hood can also applied in the first embodiment, the secondembodiment, the third embodiment, and the later-mentioned sixthembodiment.

The excitation light source 23 may be fixed to the acoustic wavegenerator 24 so as to simultaneously operate with the acoustic wavegenerator 24. For example, the excitation light source 23 may beintegrated with the acoustic wave generator 24. Because the excitationlight source 23 simultaneously operates with the acoustic wave generator24, the excitation light source 23 can automatically be moved to theposition suitable to the measurement. The fifth embodiment shows themode in which the excitation light source 23 outputs one light beam.However, the excitation light source 23 can also emit the two lightbeams having the mutually different wavelengths λ₁ and λ₂ and output theintensity modulated light beams having the same frequency and reversephases. As described in the first embodiment to the fourth embodiment,the two light beams having the mutually different wavelengths in whichthe frequencies are equal to each other and the phases are reversed toeach other are used as the intensity modulated light 1, which allows theinfluence of the water on the photoacoustic signal to be removed.

The acoustic wave generator 24 shown in FIG. 34 generates and outputsthe acoustic wave 2 which is of the ultrasonic wave. The frequency ofthe ultrasonic wave generated by acoustic wave generator 24 generatesthe frequency of the photoacoustic signal 3 generated by the living bodytest region 97. For example, the acoustic wave generator, whichgenerates the acoustic wave having the frequency of about 200 kHz, maybe used as acoustic wave generator 24.

Preferably, in the acoustic wave generator 24, the frequency and/orintensity of the outputted acoustic wave 2 is variable. When thefrequency of the outputted acoustic wave 2 is variable, the frequency ofthe photoacoustic signal 3 in which the generated frequency is changedby the change of the living body test region 97 can be outputted fromthe acoustic wave generator 24. When the intensity of the outputtedacoustic wave 2 is variable, the intensity of the acoustic wave 2outputted from the acoustic wave generator 24 can be decreased andincreased according to the intensity of the acoustic wave 2 detected byultrasonic detector 25, so that the intensity can be compared even ifthe intensity detected by the acoustic wave detector 25 is small.

FIG. 35 is a schematic view showing examples of the acoustic wavegenerator 24 and the acoustic wave detector 25, FIG. 35( a) is anexternal view, FIG. 35( b) is a top view of the acoustic wave generator,FIG. 35( c) is a perspective view of the acoustic wave generator, andFIG. 35( d) is a bottom view of the acoustic wave generator. FIG. 35( a)shows the state in which the living body test region 97 is clamped bythe acoustic wave generator 24 in which the acoustic coupling element 28is arranged and the acoustic wave detector 25 in which the acousticcoupling element 28 is arranged. As shown in FIGS. 35( b), 35(c), and35(d), the transmission window 29 which transmits the intensitymodulated light beam may be further included in a part of the acousticwave generator 24. The transmission window 29 may be used as a throughhole. A transparent member, which is transparent to the intensitymodulated light, may be arranged in the surface which is in contact withthe living body test region 97. The acoustic coupling element 28 may beused as the transparent member. Thus, the transmission window 29 isfurther included, the acoustic wave generator 24 is arranged between theexcitation light source and the living body test region 97, and therebythe living body test region 97 can be irradiated from above the acousticwave generator 24. Accordingly, because the living body test region 97can be irradiated with the intensity modulated light at thesubstantially same position as the position where the acoustic wavesuitable to the measurement is outputted, the living body test region 97can be irradiated with the intensity modulated light such that thephotoacoustic signal propagates in the propagation path suitable to themeasurement. The propagation path suitable to the measurement isconfirmed by the acoustic wave.

The acoustic wave detector 25 shown in FIG. 34 detects the acoustic wave2 and the photoacoustic signal 3 which are of the ultrasonic wave. Theacoustic wave detector 25 also includes one which detects thephotoacoustic signal 3 to output the electric signals proportional tothe acoustic pressures of the acoustic wave 2 and the photoacousticsignal 3 as the output signal 4. Examples of the acoustic wave detector25 include the acoustic wave detector such as a crystal microphone, aceramic microphone, and a ceramic ultrasonic wave sensor in which themagneto-striction effect or electro-striction effect is utilized, theacoustic wave detector such as a moving-coil microphone and a ribbonmicrophone in which electromagnetic induction is utilized, the acousticwave detector such as a capacitor microphone in which electrostaticeffect is utilized, and the acoustic wave detector such as amagneto-striction vibrator in which magneto-striction is utilized. Thefrequency flat type electro-striction device (ZT) and the acoustic wavedetector including the crystal such as PVDF (polyvinylidene fluoride)can be cited as an example of the acoustic wave detector in which thepiezoelectric effect is utilized. PZT into which the FET (Field EffectTransistor) amplifier is incorporated may be used as acoustic wavedetector 25.

The acoustic coupling element 28 shown in FIG. 34 is a member having thesubstantially equal acoustic impedance as the living body test region97. Examples of the acoustic matching substance include rubber, a softsolid such as resin, a liquid, and sol or gel. Preferably, the acousticcoupling element 28 is arranged in the surface in which at least one ofthe acoustic wave generator 24 and the acoustic wave detector 25 is incontact with living body test region 97, and the reflection/scatteringcan be decreased at the surface which is in contact with the living bodytest region by arranging the acoustic coupling element 28.

The drive unit 27 shown in FIG. 34 moves the position at least one ofthe acoustic wave generator 24 and the acoustic wave detector 25. Forexample, the excitation light source 23 and the acoustic wave generator24 may be fixed by a structure such that the optical axis of theexcitation light source 23 coincides with the transmission window 29 ofthe acoustic wave generator 24, and the excitation light source 23 andthe acoustic wave generator 24 may be rotated around the living bodytest region 97 while the positions of the excitation light source 23 andthe acoustic wave generator 24 are maintained. The excitation lightsource 23 and the acoustic wave generator 24 may be moved on thecircumference. The distance between the excitation light source 23 andthe acoustic wave generator 24 may be varied on the circumference. Theexcitation light source 23 and the acoustic wave generator 24 may bemoved on the surface which is in contact with the living body testregion 97. The excitation light source 23 and the acoustic wavegenerator 24 may three-dimensionally be moved. In FIG. 34, the specificdrive mechanism of the drive unit 27 is neglected.

In the drive unit 27, the acoustic wave detector 25 may be fixed whilethe acoustic wave generator 24 is movable. The acoustic wave generator24 may be fixed while the acoustic wave detector 25 is movable. Both theacoustic wave generator 24 and the acoustic wave detector 25 may bemovable. In the drive unit 27, the excitation light source 23 may bemovable. In the drive unit 27, the excitation light source 23 may bemoved while simultaneously operating with the acoustic wave generator24. Because the excitation light source 23 simultaneously operates withthe acoustic wave generator 24, the excitation light source 23 canautomatically be moved to the position suitable to the measurement. Thedrive unit 27 may be operated by an instruction from the control unit26.

The acoustic wave generator 24 is moved with the drive unit 27 byincluding the above-described drive unit 27, and the influence of thescatterer can be examined in each region in the living body test region97 using the acoustic wave 2. Therefore, a transmission property of thephotoacoustic signal 3 can be estimated in the propagation path of thephotoacoustic signal 3. At least one of the irradiation angle and theirradiation position of the intensity modulated light 1 to the livingbody test region 97 is changed by moving the excitation light source 23in conjunction with the acoustic wave generator 24, the acoustic wave 2is monitored in each case such that the acoustic wave 2, which reachesthe acoustic wave detector 25 from the acoustic wave generator 24,becomes a particular value, and the influence of the reflected/scatteredscatterer on the photoacoustic signal is detected in each propagationpath. Therefore, the photoacoustic signal can be detected in thedetected optimum arrangement.

The control unit 26 shown in FIG. 34 controls the drive unit 27 suchthat the intensity of the acoustic wave 2 detected by the acoustic wavedetector 25 becomes the particular value. For example, the control unit26 determines the position where the intensity of the acoustic wave 2becomes the particular value from the signal intensity of the outputsignal 4 having the signal intensity which is outputted from theacoustic wave detector 25 and proportional to the acoustic pressure ofthe acoustic wave 2, and the control unit 26 outputs the control signal5 to the drive unit 27. The particular value is, the maximum value inthe acoustic waves 2 detected by the acoustic wave detector 25. Thephotoacoustic signal 3 can be detected in the arrangement in which thereflection/scattering become the minimum by setting the acoustic wave 2at the maximum value. The particular value may be a value which ispreviously determined before the measurement. When the predeterminedvalue is set at the particular value, the acoustic wave 2 having theconstant intensity is outputted, the propagation path is scanned suchthat the acoustic wave 2 is detected in the predetermined intensity, andthe photoacoustic signal 3 is detected in the propagation path.Therefore, the photoacoustic signals 3 having the substantially sameinfluence of reflection/scattering can be detected. Accordingly, thephotoacoustic signal 3 can automatically be detected in the detectedoptimum arrangement.

For example, a comparison circuit which compared two degrees or more ofsignal intensity, can be used as the comparison of the signal intensity.The output signals 4 to be compared may be electric signals convertedinto direct-current signals with a smoothing circuit. The drive unit maybe controlled by a small oscillation method in which the twoconsecutively detected degrees of signal intensity are compared to movethe drive unit toward the direction having the larger signal intensity.

Either the excitation light source 23 or the acoustic wave detector 25may be moved by the control signal 5. In the case where the excitationlight source 23 and the acoustic wave generator 24 are integrated, theacoustic wave generator 24 may be moved by the control signal 5. Theexcitation light source 23, the acoustic wave generator 24, and theacoustic wave detector 25 may be moved by the control signal 5. Thedrive unit 27 is controlled such that the intensity of the acoustic wave2 detected by the acoustic wave detector 25 becomes the particularvalue, which allows the photoacoustic signal 3 to be automaticallydetected in the optimum propagation path.

An operation of the blood constituent concentration measuring apparatuswill be described with reference to FIG. 34. The living body test region97 such as the finger is inserted between the acoustic wave generator 24and the acoustic wave detector 25, and the drive unit 27 brings theacoustic wave generator 24 and the acoustic wave detector 25 intocontact with living body test region 97. Then, the acoustic wave 2 isgenerated and outputted from the acoustic wave generator 24. Theoutputted acoustic wave 2 is transmitted through the acoustic couplingelement 28 arranged in the acoustic wave generator 24, the living bodytest region 97, and the acoustic coupling element 28 arranged in theacoustic wave detector 25, and the outputted acoustic wave 2 is detectedby the acoustic wave detector 25. The detected acoustic wave 2 isconverted into the electric signal proportional to the acousticpressure, a phase sensitive amplifier (not shown) included in theacoustic wave detector 25 performs the integration and averagingprocesses to the electric signal, and the output signal 4 is outputted.The control unit 26 obtains the output signal 4 as a reference signal ina first state set by the drive unit 27. Then, the control unit 26 sets asecond state in which the output position is changed with respect to theliving body test region 97 by the drive unit 27, and the samemeasurement as the first state is performed. Thus, the control unit 26obtains the reference signal in each output position. When the acousticwave 2 is detected predetermined times or in the predetermined range,the operation of the acoustic wave generator 24 is stopped.

The control unit 26 compares the degrees of intensity in each time ofthe detection of the reference signal to specify the position where theintensity of the particular value is obtained. At this point, it isassumed that the particular value is the maximum value in the acousticwaves 2 detected by the acoustic wave detector 25. The control unit 26outputs the control signal 5 to the drive unit 27 such that thedetection can be performed at the position where the intensity of theparticular value is obtained. The drive unit 27 moves the excitationlight source 23, the acoustic wave generator 24, and the acoustic wavedetector 25 to positions such that the detection can be performed at theposition where the intensity of the particular value is obtained. Theexcitation light source 23 outputs the intensity modulated light 1 fromthe moved position. The intensity modulated light 1 is transmittedthrough the transmission window 29, and the living body test region 97is irradiated with the intensity modulated light 1. The photoacousticsignal 3 generated in the living body test region 97 is detected by theacoustic wave detector 25. Similarly to the acoustic wave 2, thedetected photoacoustic signal 3 is outputted as the output signal 4 fromthe acoustic wave detector 25. The drive unit 27 may change not theoutput position of the acoustic wave 2 outputted from the acoustic wavegenerator 24, but the output angle to the living body test region 97.The photoacoustic signal 3 is detected by the above operation, whichallows the photoacoustic signal 3 to be detected in the arrangement inwhich the influences of the reflection/scattering become the minimum.

Another operation of the blood constituent concentration measuringapparatus will further be described with reference to FIG. 34. Theliving body test region 97 such as the finger is inserted between theacoustic wave generator 24 and the acoustic wave detector 25, and thedrive unit 27 brings the acoustic wave generator 24 and the acousticwave detector 25 into contact with living body test region 97. Then, theacoustic wave 2 is generated and outputted from the acoustic wavegenerator 24. The acoustic wave 2 is transmitted through the acousticcoupling element 28 arranged in the acoustic wave generator 24, theliving body test region 97, and the acoustic coupling element 28arranged in the acoustic wave detector 25, and the outputted acousticwave 2 is detected by the acoustic wave detector 25. The detectedacoustic wave 2 is converted into the electric signal proportional tothe acoustic pressure, the phase sensitive amplifier (not shown)included in the acoustic wave detector 25 performs the integration andaveraging processes to the electric signal, and the output signal 4 isoutputted. The control unit 26 obtains the output signal 4 as thereference signal in the first state set by the drive unit 27.

Then, the operation of the acoustic wave generator 24 is stopped, andthe living body test region 97 is irradiated with the intensitymodulated light 1 which is outputted from the excitation light source 23and transmitted through the transmission window 29. Similarly to theacoustic wave 2, the photoacoustic signal 3 detected by the acousticwave detector 25 is outputted as the output signal 4 from the acousticwave detector 25. The output signal 4 from the photoacoustic signal 3becomes the actual signal in the first state. After the settings of theacoustic wave generator 24 and acoustic wave detector 25 are completedwith respect to the living body test region 97, the reference signal andthe actual signal are instantly obtained in an electronic manner, sothat the position change of the living body test region 97 caused by thebody movement is hardly generated.

Then, the control unit 26 sets the second state in which the outputangle and the output position are changed with respect to the livingbody test region 97 by the drive unit 27, and the same measurement asthe first state is performed. In this case, only the first and secondstates are illustrated. However, the measurement may be performed inthree or more states. Thus, the measurement is sequentially performed,and the actual signal corresponding to the state in which the referencesignal becomes the particular value can be utilized as the measuredvalue. The particular value may be the value which is previouslydetermined before the measurement. The photoacoustic signals 3 havingthe substantially same influence of reflection/scattering can bedetected by utilizing the actual signal corresponding to the state, inwhich the acoustic wave 2 of the predetermined signal intensity isdetected, as the measured value. Therefore, the blood constituentconcentration can be measured while the influences of many parametersassociated with the change in arrangement of the blood constituentconcentration measuring apparatus are removed.

The control method of blood constituent concentration measuringapparatus according to the fifth embodiment sequentially includes anoptimum position detection procedure and a photoacoustic signaldetection procedure. In the optimum position detection procedure, theacoustic wave generator 24 outputs the acoustic wave 2 from two or moredifferent positions to the living body test region 97 which is of thetest subject, and the acoustic wave detector 25 which is of the acousticwave detection means detects the position where the intensity of theacoustic wave 2 transmitted through the living body test region 97becomes the particular value. In the photoacoustic signal detectionprocedure, the light generating means, the light modulation means, andthe excitation light source 23 which is of the light outgoing meansirradiate the living body test region 97 with the intensity modulatedlight beams which are intensity-modulated at the constant frequency fromthe positions where the intensity of the acoustic wave 2 becomes theparticular value, and the acoustic wave detector 25 detects thephotoacoustic signal 3 emitted from the living body test region 97.

After the influence of the reflected/scattered scatterer on thephotoacoustic signal is detected in each propagation path by changingthe propagation path of the acoustic wave 2, the living body test region97 is irradiated with the intensity modulated light 1 to detect thephotoacoustic signal 3 such that the photoacoustic signal 3 propagatesthrough the path in which the intensity of the acoustic wave 2 detectedby the acoustic wave detector 25 becomes the particular value.Therefore, the photoacoustic signal can be detected in the detectedoptimum arrangement.

In the optimum position detection procedure, preferably the acousticwave generator 24 outputs the acoustic wave 2 to the surface of theliving body test region 97. Therefore, the generated acoustic wave 2 canefficiently be transmitted to the living body test region 97.

In the photoacoustic signal detection procedure, preferably theexcitation light source 23 irradiates the living body test region 97with the intensity modulated light 1 through the transmission windowwhich is provided in a part of the acoustic wave generator 24 andtransparent to the intensity modulated light 1. The excitation lightsource 23 can irradiate the living body test region 97 with theintensity modulated light 1 from above the acoustic wave generator 24.Accordingly, the living body test region 97 can be irradiated with theintensity modulated light 1 at the substantially same position as theposition of the acoustic wave generator 24 where the optimum acousticwave 2 is detected.

In the light outgoing procedure, as described above, the excitationlight source 23 generates the two light beams having the mutuallydifferent wavelengths 2 and λ₂, the excitation light source 23intensity-modulates the two light beams having the mutually differentwavelengths λ₁ and λ₂ into the intensity modulated light 1 having thesame frequency and reverse phases, and the excitation light source 23outputs the intensity modulated light 1.

In the optimum position detection procedure, preferably the acousticwave generator 24 outputs the acoustic wave 2 having the substantiallysame frequency as the frequency of the intensity modulated light 1.Because the scatterer can be detected with the acoustic wave 2 havingthe same frequency as the detected photoacoustic signal 3, the influenceof the scatterer on the photoacoustic signal 3 can be examined morecorrectly.

In the optimum position detection procedure, preferably the acousticwave generator 24 increases and decreases the intensity of the outputtedacoustic wave 2 according to the intensity of the acoustic wave 2detected by the acoustic wave detector 25. Because the intensity of theacoustic wave 2 outputted from the acoustic wave generator 24 isincreased or decreased according to the intensity of the acoustic wave 2detected by the acoustic wave detector 25, the detected intensity can becompared even if the intensity detected by the acoustic wave detector 25is small.

In the optimum position detection procedure, preferably the acousticwave generator 24 and the acoustic wave detector 25 are pressed againstthe living body test region 97 to detect the acoustic wave 2 with thepressuring force in which the pressure can be controlled. Because thepressure at which the acoustic wave generator 24 and the acoustic wavedetector 25 are pressed against the living body test region 97 isvariable, the pressure at which the acoustic wave generator 24 and theacoustic wave detector 25 come into contact with the living body testregion 97 can be maintained at a constant pressure. Therefore, theinfluence of the pressure pressing the living body test region 97 can bereduced.

The circuit diagram of the blood constituent concentration measuringapparatus shown in FIG. 34 may includes pressing means (not shown) forpressing the acoustic wave generator and the acoustic wave detectoragainst the living body test region with the pressuring force in whichthe pressure can be controlled. For example, a U-shape arm in which theacoustic wave generator and the acoustic wave detector are fixed to bothends can be used as the pressing means. The arm can change the distancebetween the acoustic wave generator and the acoustic wave detector tovary the pressure at which the acoustic wave generator and the acousticwave detector are pressed against the living body test region.Therefore, the pressure at which the acoustic wave generator and theacoustic wave detector come into contact with the living body testregion can be maintained at a constant pressure.

In FIG. 34, the living body test region 97 is set at the finger of humanbody. However, an animal, a bird, and plants such as fruit and vegetablemay be used as the object to be measured. The object to be measuredincludes a pipe through which a liquid flows and the container such as abottle and a tank in which the liquid, sol or gel is reserved. Forexample, when the object to be measured is the fruit, the sugar of thefruit can be measured in the noninvasive manner.

As described above, the blood constituent concentration measuringapparatus according to the fifth embodiment detects the arrangement inwhich the positional relationship between the generation source of thephotoacoustic signal and the acoustic wave detector becomes optimum.Therefore, the photoacoustic signal is detected in the optimumarrangement in which the scatterer such as the bone has a littleinfluence on the photoacoustic signal, and the blood constituentconcentration can be measured. The photoacoustic signal is detected inthe arrangement in which the signal intensity of the detected acousticwave becomes the predetermined value. Therefore, the blood constituentconcentration can be measured while the influences of many parametersassociated with the change in arrangement of the blood constituentconcentration measuring apparatus are removed.

EXAMPLES

Specific examples in the fifth embodiment will be described below.

First Example

A first example of the blood constituent concentration measuringapparatus according to the fifth embodiment of the invention will bedescribed with reference to FIG. 36. FIG. 36 is a circuit diagram of theblood constituent concentration measuring apparatus according to thefirst example. An acoustic wave generator 404 is connected to anoscillator 403. A hole 410 which is of the outgoing window, is made inthe acoustic wave generator 404. The hole 410 is large enough toirradiate the test subject 405 with the intensity modulated light 1 fromabove the test subject 405. The acoustic wave generator 404 generatesthe acoustic wave 2 in association with the oscillation frequency of theoscillator 403. The acoustic wave 2 passes through the test subject 405,and an acoustic wave detector 407 detects the acoustic wave 2 through anacoustic coupling element 406, and the acoustic wave detector 407converts the acoustic wave 2 into the output signal 4 proportional tothe acoustic pressure. The waveform of the output signal 4 is observedby a phase sensitive amplifier 408, and the output signal 4 is outputtedto an output terminal 409. The phase sensitive amplifier 408 istriggered by the signal synchronized with the frequency of theoscillator 403, and the phase sensitive amplifier 408 can measure theoutput signal 4 while performing the integration and averaging to theoutput signal 4. The acoustic wave 2 generated from the acoustic wavegenerator 404 is detected while the arrangement of the acoustic wavedetector 407 and the pressing force against the test subject 405 arechanged. The signal intensity of the detected acoustic wave 2 issequentially measured, and the acoustic wave detector 407 is fixed tothe position where the intensity becomes the particular value. Theoptimum arrangement among the devices is realized while avoiding theinfluence of the reflection/scattering in the living body.

On the other hand, the oscillator 403 is also connected to a drive powersupply 402. The drive power supply 402 supplies the rectangularexcitation current associated with the oscillation frequency of theoscillator 403 to a semiconductor laser device 401.

After the arrangement among the devices is calibrated, the semiconductorlaser device 401 generates the intensity modulated light 1 while theintensity modulation is performed in the frequency of the oscillator403. The test subject 405 is irradiated with the intensity modulatedlight 1 passing through the hole 410 made in the center of the acousticwave generator 404. The intensity modulated light 1 generates thephotoacoustic signal 3 in the test subject 405. The photoacoustic signal3 is detected through the acoustic coupling element 406 by the acousticwave detector 407, and the photoacoustic signal 3 is converted into theoutput signal 4 proportional to the acoustic pressure. The waveform ofthe output signal 4 is observed by the phase sensitive amplifier 408.The phase sensitive amplifier 408 is triggered by the signalsynchronized with the frequency of the oscillator 403, and the phasesensitive amplifier 408 can measure the output signal 4 while performingthe integration and averaging to the output signal 4. The measuredsignal is outputted to the outside from the output terminal 409.

In the above configuration, the acoustic wave generator 404 has thediameter of about 30 mm, the acoustic wave generator 404 has the hole inthe center, and the hole has the radius of 10 mm. The acoustic wavegenerator is brought into close contact with the test subject 405through the ultrasonic wave gel. The generated acoustic wave 2 is 200kHz, and the acoustic wave 2 is controlled by the oscillator 403.

The acoustic wave detector 407 is the frequency flat typeelectrostrictive device (PZT) into which the field effect transistor(FET) amplifier is incorporated. The ultrasonic wave gel is used as theacoustic coupling element 406. In the above configuration, the signalintensity of Vr=1 to 15 mV is obtained as the output signal 4corresponding to the acoustic wave 2 at the output terminal 409 of thephase sensitive amplifier 408 in which the time constant is set at 0.1second. Therefore, the optimum arrangement is fixed to the positionwhere Vr=15 mV is detected.

On the other hand, the wavelength of the semiconductor laser device 401is set at 1608 nm. The wavelength of 1608 nm corresponds to theabsorption wavelength of glucose. The modulation frequency in which theintensity modulated light 1 is intensity-modulated is set at 200 kHz,and the output of the intensity modulated light 1 is 5.0 mW.

The light beam diameter with which the test subject 405 is irradiated isset at 2.7 mm such that the Fresnel number becomes 0.1 while thedistance between the acoustic wave detector 407 and the position of thetest subject 405 irradiated with the beam is set at 10 mm.

In this state of things, the irradiation intensity to the skin with theoutput light of the semiconductor laser device 401 is 0.22 mW/mm² in theoutput light of the semiconductor laser device 401, and the irradiationintensity is in the safe level which is lower than a half of the maximumtolerance. However, preferably the light shielding hood (not shown) isplaced at the position where the test subject 405 is arranged such thatthe light is reflected or scattered from the acoustic coupling element406 does not leak outside during the measurement or during the testsubject 405 is not placed.

The acoustic wave detector 407 is the frequency flat typeelectrostrictive device (PZT) into which the field effect transistor(FET) amplifier is incorporated. The ultrasonic wave gel is used as theacoustic coupling element 406. In the above configuration, in the casewhere the test subject 405 is irradiated only with the intensitymodulated light 1 outputted from the semiconductor laser device 401, thesignal intensity of Vr=20 μV is obtained as the output signal 4corresponding to the photoacoustic signal 3 at the output terminal 409of the phase sensitive amplifier 408 in which the time constant is setat 0.1 second.

Thus, before the photoacoustic measurement, the arrangement iscalibrated using the acoustic wave 2 generated by the acoustic wavegenerator 404 as the reference signal, the output signal 4 proportionalto the acoustic pressure of the photoacoustic signal 3 is measured bythe semiconductor laser device 401, and the photoacoustic signal 3corresponding to the glucose absorption in the test subject 405 ismeasured.

Second Example

A second example will be described with reference to FIG. 36. Theacoustic wave generator is connected to the oscillator. The hole is madein the acoustic wave generator 404, and the hole is large enough toirradiate the test subject 405 with the excitation light from above thetest subject 45.

The acoustic wave generator 404 generates the acoustic wave 2 inassociation with the oscillation frequency of the oscillator 403. Theacoustic wave 2 passes through the test subject 405, and the acousticwave detector 407 detects the acoustic wave 2 through the acousticcoupling element 406, and the acoustic wave detector 407 converts theacoustic wave 2 into the output signal 4 proportional to the acousticpressure. The phase sensitive amplifier 408 can measure the waveform ofthe output signal 4 while performing the integration and averaging tothe output signal 4. The acoustic wave 2 generated from the acousticwave generator 404 is detected while the arrangement of the acousticwave detector 407 and the pressing force against the test subject 405are changed. The signal intensity of the detected acoustic wave 2 issequentially measured, and the acoustic wave detector 407 is fixed tothe position where the intensity becomes the particular value. Theoptimum arrangement among the devices is realized while avoiding theinfluence of the reflection/scattering in the living body.

On the other hand, the oscillator 403 is also connected to the drivepower supply 402. The drive power supply 402 supplies the rectangularexcitation current to the semiconductor laser device 401.

After the arrangement among the devices is calibrated, the semiconductorlaser device 401 generates the intensity modulated light 1 while theintensity modulation is performed in the frequency of the oscillator403. The test subject 405 is irradiated with the intensity modulatedlight 1 passing through the hole 410 made in the center of the acousticwave generator 404. The intensity modulated light 1 generates thephotoacoustic signal 3 in the test subject 405. The photoacoustic signal3 is detected through the acoustic coupling element 406 by the acousticwave detector 407, and the photoacoustic signal 3 is converted into theoutput signal 4 proportional to the acoustic pressure. The waveform ofthe output signal 4 is observed by the phase sensitive amplifier 408.The phase sensitive amplifier 408 is triggered by the signalsynchronized with the frequency of the oscillator 403, and the phasesensitive amplifier 408 can measure the output signal 4 while performingthe integration and averaging to the output signal 4. The measuredsignal is outputted to the outside from the output terminal 409.

In the above configuration, the acoustic wave generator 404 has thediameter of about 30 mm, the acoustic wave generator 404 has the hole inthe center, and the hole has the radius of 10 mm. The acoustic wavegenerator is brought into close contact with the test subject 405through the ultrasonic wave gel. The generated acoustic wave 2 is 200kHz, and the acoustic wave 2 is controlled by the oscillator 403.

The acoustic wave detector 407 is the frequency flat typeelectrostrictive device (PZT) into which the FET (Field EffectTransistor) amplifier is incorporated. The ultrasonic wave gel is usedas the acoustic coupling element 406. In the above configuration, thesignal intensity of Vr=1 to 15 mV is obtained as the output signal 4corresponding to the acoustic wave 2 at the output terminal 409 of thephase sensitive amplifier 408 in which the time constant is set at 0.1second. Therefore, the optimum arrangement is fixed to the positionwhere Vr=15 mV is detected.

On the other hand, the wavelength of the semiconductor laser device 401is set at 1608 nm. The wavelength of 1608 nm corresponds to theabsorption wavelength of glucose. The intensity modulation frequency isset at 200 kHz, and the output is 5.0 mW.

The beam diameter of the intensity modulated light 1 with which the testsubject 405 is irradiated is set at 2.7 mm such that the Fresnel numberN becomes 0.1 while the distance between the acoustic wave detector 407and the position of the test subject 405 irradiated with the beam is setat 10 mm.

In this state of things, the irradiation intensity to the skin of thetest subject 405 with the output light of the semiconductor laser device401 is 0.22 mW/mm², and the irradiation intensity is in the safe levelwhich is lower than a half of the maximum tolerance. However, preferablythe light shielding hoods (not shown) is placed at the position wherethe test subject 405 is arranged such that the light reflected orscattered from the acoustic coupling element 406 does not leak outsideduring the measurement or during the test subject 405 is not placed.

The acoustic wave detector 407 is the frequency flat typeelectrostrictive device (PZT) into which the FET (Field EffectTransistor) amplifier is incorporated. The ultrasonic wave gel is usedas the acoustic coupling element 406. In the above configuration, in thecase where the test subject 405 is irradiated only with the intensitymodulated light 1 outputted from the semiconductor laser device 401, thesignal intensity of Vr=20 μV is obtained as the output signal 4corresponding to the photoacoustic signal 3 at the output terminal 409of the phase sensitive amplifier 408 in which the time constant is setat 0.1 second.

After the above measurement is performed, the measuring apparatus isdetached, and the same measurement is performed again. The acoustic wave2 generated from the acoustic wave generator 404 is detected while thearrangement of the acoustic wave detector 407 and the pressing forceagainst the test subject 405 are changed. The signal intensity of Vr=1to 15 mV is obtained as the output signal 4 corresponding to theacoustic wave 2 at the output terminal 409 of the phase sensitiveamplifier 408 in which the time constant is set at 0.1 second.Therefore, the optimum arrangement is fixed to the position where Vr=15mV is detected.

When the photoacoustic signal 3 generated by the semiconductor laserdevice 401 is measured at the fixed position using the phase sensitiveamplifier 408, the signal intensity of Vr=20 μV is obtained.

Thus, in performing the re-measurement, the arrangement is calibrated byutilizing the acoustic wave 2 generated by the acoustic wave generator404 as the reference signal, which allows the measurement to beperformed with good reproducibility for the measurement of thephotoacoustic signal 3.

Sixth Embodiment

A blood constituent concentration measuring apparatus according to asixth embodiment includes light generating means for generating twolight beams having different wavelengths; light modulation means forelectrically intensity-modulating each of the two light beams having themutually different wavelengths using signals having the same frequencyand reverse phases; light outgoing means for multiplexing into one lightflex to output the intensity-modulated two light beams having themutually different wavelengths toward a living body; acoustic wavedetection means for detecting an acoustic wave generated in the livingbody by the outputted light; and enduing means for mounting at least thelight outgoing means and the acoustic wave detection means, the enduingmeans having an annular portion in which the living body is fitted whilesurrounding the living body. The blood constituent concentrationmeasuring apparatus of the sixth embodiment is characterized in that thelight outgoing means and the acoustic wave detection means are arrangedinside the annular portion of the enduing means in a portion which is incontact with the living body. The enduing means according to the sixthembodiment can also applied in the blood constituent concentrationmeasuring apparatus according to the first embodiment, the secondembodiment, the third embodiment, the fourth embodiment, and the fifthembodiment.

Particularly, in the blood constituent concentration measuring apparatusaccording to the sixth embodiment, the light generating meanseffectively sets one of the light wavelengths of the two light beams atthe wavelength in which the blood constituent exhibits thecharacteristic absorption, and the light generating means effectivelysets the other light wavelength at the wavelength in which the waterexhibits the absorption parallelly equal to that in one of the lightwavelengths.

A basic configuration of a measuring system of the blood constituentconcentration measuring apparatus according to the sixth embodiment willbe described with reference to FIG. 37. FIG. 37 shows the basicconfiguration of the measuring system of the blood constituentconcentration measuring apparatus according to the sixth embodiment. Thecomponents concerning the later-mentioned mounting technique and thecomponents, such as a power supply, which can be realized by theconventional techniques are not shown in FIG. 37.

In FIG. 37, the first light source 101 which is of a part of the lightgenerating means is intensity-modulated in synchronization with theoscillator 103 which is of a part of the light modulation means by thedrive circuit 1.04 which is of a part of the light modulation means.

On the other hand, the second light source 105 which is of a part of thelight generating means is intensity-modulated in synchronization withthe oscillator 103 which is of a part of the light modulation means bythe drive circuit 108 which is of a part of the light modulation means.However, the output of the oscillator 103 is supplied to the drivecircuit 108 through the 180°-phase-shift circuit 107 which is of a partof the light modulation means. As a result, the second light source 105is configured so as to be intensity-modulated with the signal whosephase is changed by 180° with respect to the light source 101.

In the wavelengths of the first light source 101 and the second lightsource 105 shown in FIG. 37, one of the light wavelengths of the twolight beams is set at the wavelength in which the blood constituentexhibits the characteristic absorption, and the other light wavelengthis set at the wavelength in which the water exhibits the absorptionparallelly equal to that in one of the light wavelengths.

By way of example, in the case where the blood constituent of themeasuring object is set at glucose, i.e., in the case where the bloodsugar level is measured, it is effective that the wavelength (λ₁) of thefirst light source 101 is set at 1608 nm and the wavelength (λ₂) of thesecond light source 105 is set at 1381 nm. In the case of the longerwavelength band, it is effective that the wavelength (λ₁) of the firstlight source 101 is set at 2126 nm and the wavelength (λ₂) of the secondlight source 105 is set at 1837 nm or 2294 nm. FIG. 7 shows arelationship between the wavelength (λ₁) of the first light source 101and the wavelength (λ₂) of the second light source 105.

The first light source 101 and the second light source 105 output thelight beams having the different wavelengths respectively, the outputtedlight beams are multiplexed into one light flux by the coupler 109 whichis of the light outgoing means, and the multiplexed light is outputtedto the living body test region 110. The acoustic waves, i.e., thephotoacoustic signals generated in the living body test region 110 bythe light beams outputted from the first light source 101 and the secondlight source 105 are detected by the ultrasonic detector 113 which is ofa part of the acoustic wave detection means, and the photoacousticsignals are converted into the electric signals proportional to theacoustic pressures of the photoacoustic signals. The phase sensitiveamplifier 114 which is of a part of the acoustic wave detection meanssynchronized with the oscillator 103 performs the synchronous detectionto the electric signal, and the electric signal proportional to theacoustic pressure is outputted to the output terminal 115.

At this point, the intensity of the signal outputted to the outputterminal 115 is proportional to a light quantity in which the light beamoutputted from each of the first light source 101 and the second lightsource 105 is absorbed by the constituent in the living body test region110, so that the signal intensity is proportional to the mount ofconstituent in the living body test region 110. Accordingly, the bloodconstituent concentration computation means (mot shown) computes themount of constituent of the measuring object in the blood of the livingbody test region 110 from the measured value of the intensity of thesignal outputted to the output terminal 115.

In the blood constituent concentration measuring apparatus according tothe embodiment, the two light beams having the different wavelengthsoutputted from the first light source 101 and the second light source105 are intensity-modulated using the signals having the same period,i.e., the same frequency. Therefore, the blood constituent concentrationmeasuring apparatus according to the sixth embodiment has a feature thatthe blood constituent concentration measuring apparatus according to thesixth embodiment is not affected by the unevenness of the frequencycharacteristics of the ultrasonic detector 113. This is the excellentpoint as compared with the currently existing techniques.

In the blood constituent concentration measuring apparatus according tothe sixth embodiment, the light modulation means is effectively formedby light modulation means for performing the modulation at the samefrequency as the resonant frequency concerning the detection of theacoustic wave generated in the living body.

Thus, the two light beams having different wavelengths is modulated withthe same frequency as the resonant frequency concerning the detection ofthe acoustic wave generated in the living body, which allows theacoustic wave generated in the living body to be detected with highsensitivity.

On the other hand, the non-linear absorption coefficient dependenceexisting in the measured value of the photoacoustic signal, whichbecomes troublesome in the conventional technique, can be solved byperforming the measurement using the light beams having the pluralwavelengths for giving the equal absorption coefficient in the bloodconstituent concentration measuring apparatus according to the sixthembodiment. That will be described below.

That is, in the case where background absorption coefficients α₁ ^((b)),α₂ ^((b)) and molar absorptions α₁ ⁽⁰⁾, α₂ ⁽⁰⁾ of the blood constituentset as the measuring object are already known for light beams having awavelength λ₁ and a wavelength λ₂ respectively, the simultaneousequations including measured values s₁ and s₂ of the photoacousticsignal in the wavelengths are expressed by the formula (1).

The unknown blood constituent concentration M is determined by solvingthe formula (1). Where C is a variable coefficient which is hardlycontrolled or calculated, i.e., C is an unknown multiplier depending onan acoustic coupling state, ultrasonic detector sensitivity, a distancebetween the light outgoing means and the acoustic wave detection means(hereinafter defined as r), specific heat, a thermal expansioncoefficient, sound velocity, the modulation frequency, and theabsorption coefficient.

When the difference is generated in C of the first line and the secondline of the formula (1), the difference is an amount concerning theirradiation light, i.e., the difference by the absorption coefficient.At this point, when a combination of the wavelength λ₁ and thewavelength λ₂ is selected such that the parentheses of the lines of theformula (1), i.e., the absorption coefficients are equal to each other,the absorption coefficients are equal to each other, and C in the firstline is equal to C in the second line. However, when the above operationis exactly performed, it is inconvenient because the combination of thewavelength λ₁ and the wavelength λ₂ depends on the unknown bloodconstituent concentration M.

At this point, the background (α_(i) ^((b)), i=1 and 2) is remarkablylarger than a term (Mα_(i) ⁽⁰⁾) including the blood constituentconcentration M in an occupying ratio in the absorption coefficient(parenthesis in each line) of the formula (1). That is, the two lightbeams having the mutually different wavelength λ₁ and wavelength λ₂ maybe selected such that the absorption coefficients α₁ ^((b)) and α₂^((b)) of the background are equal to each other. Thus, when C in thefirst line is equalized to C in the second line, Cs are deleted as anunknown constant, and the blood constituent concentration M of themeasuring object is expressed by the following formula (4). In thedeformation of the rear stage of the formula (4), quality of s₁≅s₂ isused.

Referring to the formula (4), in the denominator, the difference inabsorption coefficient of the blood constituent of the measuring objectemerges in wavelength λ₂ and wavelength λ₂. As the difference isincreased, the difference signal s₁−s₂ of the photoacoustic signal isincreased, and the measurement becomes easy. In order to maximize thedifference, the wavelength in which the constituent absorptioncoefficient α₁ ⁽⁰⁾ of the measuring object becomes the maximum isselected as the wavelength λ₁, and the wavelength in which α₂ ⁽⁰⁾=0,i.e., the constituent of the measuring object does not exhibit theabsorption characteristics is selected as the wavelength λ₂. At thispoint, in the second wavelength λ₂, it is necessary that α₂ ^((b))=α₁^((b)), i.e., the background absorption coefficient is equal to theabsorption coefficient of the first wavelength λ₁.

In the formula (4), the photoacoustic signal s₁ emerges only in the formof the difference of s₁−s₂ between the photoacoustic signal s₁ and thephotoacoustic signal s₂. For example, when glucose is set at theconstituent of the measuring object, as described above, there is onlythe difference 0.1% or less between the intensity of the photoacousticsignal s₁ and the intensity of the photoacoustic signal s₂.

However, in the denominator of the formula (4), it is sufficient thatthe photoacoustic signal s₂ has the accuracy of about 5%. Accordingly,the accuracy is easily kept in measuring the difference s₁−s₂ betweenthe photoacoustic signal s₁ and the photoacoustic signal s₂ to dividethe measured value by the separately measured photoacoustic signal s₂rather than sequentially separately measuring the photoacoustic signals₁ and the photoacoustic signal s₂. Accordingly, in the bloodconstituent concentration measuring apparatus according to the sixthembodiment, when the light beams having the wavelength λ₁ and thewavelength λ₂ are intensity-modulated into the light beams having thereverse phases to irradiate the living body, and the difference signals₁−s₂ of the photoacoustic signals is measured. The difference signals₁−s₂ of the photoacoustic signals is generated in the living body whilethe photoacoustic signal s₁ and the photoacoustic signal s₂ are mutuallysuperposed.

As described above, in measuring the blood constituent concentration,using the two light beams having the mutually different particularwavelengths, the measurement is performed not by separately measuringthe photoacoustic signals generated in the living body, but by measuringthe difference between the photoacoustic signals, one of thephotoacoustic signals is measured while the other photoacoustic signalis set to zero, and the measured values are computed by the formula (4).Therefore, the blood constituent concentration can easily be measured.

A mounting structure of the blood constituent concentration measuringapparatus according to the sixth embodiment will be described below.FIG. 38 shows a configuration of an enduing means of the bloodconstituent concentration measuring apparatus according to the sixthembodiment. In an enduing unit 130 which is of the enduing means shownin FIG. 38, at least a light irradiation unit 133 which is of the lightoutgoing means and an ultrasonic detection unit 135 which is of theacoustic wave detection means are mounted inside an annular supportframe 132 having an annular shape surrounding a living body 131 which isof the test subject. In FIG. 38, the light irradiation unit 133 and theultrasonic detection unit 135 are mounted in the surface which is incontact with the living body 131 inside the annular support frame 132,and the light irradiation portion of the light irradiation unit 133 andthe ultrasonic wave reception portion of the ultrasonic detection unit135 are mounted while facing each other across the living body 131.

In the enduing unit 130 having the above structure, the living body 131is securely held, the movement and the change in shape of the livingbody 131 are effectively minimized, the constant thickness of the livingbody 131 is maintained between the light irradiation unit 133 and theultrasonic detection unit 135, the change in shape of the living body131 is suppressed near the ultrasonic detection unit 135, and the changein reflection of the ultrasonic wave from the living body 131 isdecreased near the ultrasonic detection unit 135. Therefore, the bloodconstituent concentration can correctly be measured.

As described above, the light irradiation unit 133 and the ultrasonicdetection unit 135 are arranged at the while substantially facing eachother in the annular portion of the enduing unit 130. Therefore, theultrasonic wave generated in the living body 131 by the light emittedfrom the light irradiation unit 133 can efficiently be detected by theultrasonic detection unit 135.

In the blood constituent concentration measuring apparatus of the sixthembodiment, preferably a cushioning material layer having the acousticimpedance close to that of the living body is arranged at least halfaround a portion which is in contact with the living body. The portionalso includes the point where the acoustic wave detection means isarranged, and the portion is located inside the annular portion of theenduing means. In the configuration of the enduing means in the bloodconstituent concentration measuring apparatus according to the sixthembodiment, as shown in FIG. 39, the layer made of a cushioning material136 having the acoustic impedance close to that of the living body isarranged at least half around the portion which is in contact with theliving body. The portion also includes the ultrasonic detection unit 135is arranged, and the portion is located inside the annular portion ofthe enduing unit 130.

When the acoustic wave is incident to the interface between the mediumshaving the acoustic impedances Z₁ and Z₂, generally the incidentacoustic wave propagates while divided into a transmitted wave and areflected wave. A ratio of the reflected wave to the incident wave ofthe acoustic pressure is called pressure reflectivity. In the case wherethe acoustic wave is normally incident to the interface, it is knownthat the pressure reflectivity is expressed by the formula (4).

Because it is known that the acoustic impedance Z₁ of the living body131 is close to that of the water, the acoustic impedance Z₁ is about1.48 MRays (1 MRays=10⁶ kg/m²·s). On the other hand, air which isnormally in contact with the surface of the living body 131, has theacoustic impedance of 4.08×104 MRays, and there is a difference morethan three figures between the acoustic impedance values. As a result,the pressure reflectivity exceeds 99.9% when the acoustic wave isnormally incident to the surface of the living body 131, and thepressure reflectivity is larger when the acoustic wave is obliquelyincident to the surface of the living body 131.

Such reflection can be reduced by utilizing the cushioning material 136having the acoustic impedance close to that of the living body 131 toperform the acoustic matching. For example, silicone rubber which is notharmful to the living body 131 and is also used in a human body embeddedtype medical tool typically has the acoustic impedance of 1.24 MR. Thepressure reflectivity can be reduced to about 9% at the interfacebetween air and the living body 131 by utilizing the silicone rubber asthe cushioning material 136.

In the noninvasive blood constituent concentration measuring apparatusaccording to the sixth embodiment, the living body 131 is irradiatedwith the light having the wavelength 1 μm or longer. In this case,because the moisture occupying the large part of the living body 131exhibits the strong absorption, a sound source is locally formed nearthe skin surface immediately below the living body 131 of the regionirradiated with the light from the light irradiation unit 133, and thegenerated ultrasonic wave can be regarded as the spherical wave.

As described later, because the light beam diameter of the lightirradiation unit 133 is enlarged to about 5 mm, the sound source formedby the irradiation light exhibits a disc shape, and the thickness of thedisc depends on the absorption length α⁻¹ of the living body 131. In thelight irradiation having the wavelength of about 1.6 μm, the thicknessof the disc becomes about 1.6 mm. In the light irradiation having thewavelength of about 2.1 μm, the thickness of the disc becomes about 0.4mm.

Because the sound source exhibits the thin disc shape, directivity isgenerated in the ultrasonic wave, and the ultrasonic wave generated inthe living body 131 propagates in a focused way toward the direction ofthe ultrasonic detection unit 135. Accordingly, it is effective that thecushioning material 136 is arranged at least half around the portionwhich is in contact with the living body while including the ultrasonicdetection unit 135. The portion is located inside the annular portion ofthe enduing unit 130.

As described above, the layer made of the cushioning material 136 havingthe acoustic impedance close to that of the living body 131 is arrangedat least half around the portion which is in contact with the livingbody 131. The portion also includes the ultrasonic detection unit 135 tobe arranged, and the portion is located inside the annular portion ofthe enduing unit 130. Therefore, in the ultrasonic wave generated in theliving body 131 by the light emitted from the light irradiation unit133, the portion of the ultrasonic wave which directly reaches theultrasonic wave detection unit 135, is efficiently detected by theultrasonic detection unit 135. Further, the amount of ultrasonic wavewhich is received by the ultrasonic detection unit 135 as a noise afterthe multiple reflection is generated at the interface between the livingbody 131 and the inside of the annular support frame 132 of the enduingunit 130 is decreased. Accordingly, the blood constituent concentrationcan be measured more correctly.

In the blood constituent concentration measuring apparatus according tothe sixth embodiment, the gap between the cushioning material layer andthe surface inside the annular portion of the enduing means can befilled with the sound absorbing material. As shown in FIG. 40, in theconfiguration of the enduing means in the blood constituentconcentration measuring apparatus according to the sixth embodiment, thegap between the cushioning material 136 and the surface inside theannular support frame 132 of the annular portion of the enduing unit 130can be filled with the sound absorbing material 137. The material whichwell absorbs the ultrasonic wave is used as the sound absorbing material137. For example, in the case where the silicone rubber is used as thecushioning material 136, assuming that the gap is not filled with thesound absorbing material 137, when the ultrasonic wave traveling in thecushioning material 136 reaches the annular support frame 132 made ofmetal, the ultrasonic wave is reflected by the surface of the annularsupport frame 132 because the pressure reflectivity is about 60% betweenthe silicone rubber and the metal. Then, the ultrasonic wave reverselytravels in the silicone rubber of the cushioning material 136, and theultrasonic wave reaches the living body 131 again.

In order to prevent the above reflection, it is effective that thematerial in which the metal oxide powders (titanium oxide or tungstenoxide) are included in the epoxy resin is used as the sound absorbingmaterial 137.

As described above, the gap between the cushioning material 136 and thesurface inside the annular support frame 132 of the annular portion ofthe enduing unit 130 is filled with the sound absorbing material 137,which reduces the amount of ultrasonic wave, which is detected as thenoise by the ultrasonic detection unit 135 after the ultrasonic wavegenerated in the living body 131 by the light emitted from the lightirradiation unit 133 is reflected from the interface between thecushioning material 136 and the annular support frame 132. Therefore,the blood constituent concentration can correctly be measured.

In the blood constituent concentration measuring apparatus according tothe sixth embodiment, the light generating means can be formed by thelight generating means in which the two light beams having differentwavelengths are generated by plural semiconductor laser devices.

As described above, the light generating means generates the two lightbeams having different wavelengths with the plural semiconductor laserdevices, which allows the significant miniaturization and weightreduction to be achieved in the blood constituent concentrationmeasuring apparatus according to the sixth embodiment.

In the blood constituent concentration measuring apparatus according tothe sixth embodiment, preferably the light outgoing means includes abeam diameter enlarger which enlarges the light beam diameter generatedby the light generating means.

As described above, the light outgoing means includes a beam diameterenlarger which enlarges the light beam diameter generated by the lightgenerating means. Therefore, the light beam outputted to the living bodyis enlarged, and the relatively strong light can be outputted withoutaffecting the reverse influence on the living body. Accordingly, theblood constituent concentration of the living body can be measured morecorrectly.

In the blood constituent concentration measuring apparatus according tothe sixth embodiment, the enduing means is a ring in which the finger ofthe human body is fitted, and the enduing means can be formed in theenduing means in which the light outgoing means is arranged on thedorsal side of the finger while the acoustic wave detection means isarranged on the palm side of the finger.

As described above, the enduing means is the ring in which the finger ofthe human body is fitted, the light outgoing means is arranged on thedorsal side of the finger, and the acoustic wave detection means isarranged on the palm side of the finger. Therefore, the acoustic wavedetection means easily comes into contact with the relatively soft skinin the finger, and the acoustic wave detection means can efficientlymeasure the ultrasonic wave generated in the finger, so that the bloodconstituent concentration can be measured more correctly. Further, thelight outgoing means and the acoustic wave detection means are mountedin the inner surface of the ring, which allows the blood constituentconcentration of the human body to be easily and continuously measuredwithout causing difficulties in a daily life.

In the blood constituent concentration measuring apparatus according tothe sixth embodiment, the enduing means is a bracelet in which the armof the human body is fitted, and the enduing means can be formed in theenduing means in which the light outgoing means is arranged on the palmside of the hand while the acoustic wave detection means is arranged onthe dorsal side of the hand.

As described above, the enduing means is the bracelet in which the armof the human body is fitted, the light outgoing means is arranged on thepalm side of the hand, and the acoustic wave detection means is arrangedon the dorsal side of the hand. Therefore, the acoustic wave detectionmeans easily comes into contact with the relatively soft skin of thearm, and the acoustic wave detection means can efficiently measure theultrasonic wave generated in the arm, so that the blood constituentconcentration can be measured more correctly. Further, the lightoutgoing means and the acoustic wave detection means are mounted in theinner surface of the bracelet, which allows the constituentconcentration of the human body to be easily and blood continuouslymeasured without causing difficulties in a daily life.

EXAMPLES

Specific examples in the sixth embodiment will be described below.

First Example

FIG. 41 shows a first example in which the blood constituentconcentration measuring apparatus according to the sixth embodiment isapplied to the human body to realize the enduing means as the ring.

FIG. 41 shows a first example in which the blood constituentconcentration measuring apparatus according to the sixth embodiment isfitted to the hand. In FIG. 41, the light outgoing means and theacoustic wave detection means are embedded in the enduing unit 207 whichis of the ring type the enduing means in which the living body 193 whichis of the test subject is fitted, and the power supply phase, the phasesensitive amplifier, and the blood constituent concentration detectionmeans are incorporated into a wristwatch type display unit 221. Thepower supply supplies the electric power to the light outgoing means andthe acoustic wave detection means. The phase sensitive amplifier whichis of a part of the acoustic wave detection means amplifies the electricsignal outputted from the ultrasonic detector which is of a part of theacoustic wave detection means. The enduing unit 207 and the display unit221 are connected with the connection cable 210.

A display device which plays the measured blood constituentconcentration, is provided outside the display unit 221, and at leastone button for starting the measurement is also provided. A timemeasuring function, a function of storing and reading the measurementconcentration data, and a communication function of transmitting thestored measured data to the external device are also effectivefunctions.

Desirably the connection cable 210 has stretching properties so as notto block the hand movement, and the connection cable 210 is arrangedbetween the finger extensor tendons in the dorsal of the hand. In FIG.41, the second finger of the left hand is fitted in the enduing unit207. However, obviously the enduing unit 207 may be formed such that anyfinger of the hand can be fitted in.

FIG. 42 is a view showing a state in which the ring type enduing unit207 is detached from the finger, and FIG. 42 shows a state in which theconnection cable 210 is placed in a ring frame 222. In order to hold theconnection cable 210 between the tendons of the fingers, a lead-outportion of the connection cable 210 is provided in the enduing unit 207while biased from the top of a bezel of the ring. FIG. 43 show asectional view taken on broken line a-a of FIG. 42, i.e., the center ofthe width of the frame 222.

In the section of the enduing unit 207 of FIG. 43, a light source chip314 which is of a part of the light generating means and an irradiationwindow 313, a reflecting mirror 316, and a concave mirror 317, whichconstitute the light outgoing means, are placed in the portioncorresponding to the bezel of the ring which is located on the dorsalside (upward direction of FIG. 43) of the finger during the fitting. Onthe other hand, an ultrasonic detector 305 which is of a part of theacoustic wave detection means is placed in the portion on the palm side(downward direction of FIG. 43) of the finger

Because the ultrasonic detector 305 has the high output impedance, fromthe viewpoint of noise, it is inadvisable that the output is directlyguided to the display unit 221 shown in FIG. 41 through the connectioncable 310. Therefore, a preamplifier 312 is placed close to theultrasonic detector 305 which converts the impedance, the preamplifier312 is connected to the output terminal of the ultrasonic detector 305to convert the output impedance of the ultrasonic detector 305 intolower level, and the output signal of the preamplifier 312 is suppliedto the display unit 221 through the connection cable 210 shown in FIG.41.

The countermeasures for reflection of the ultrasonic wave are made onboth sides of the ultrasonic detector 305 as shown in FIG. 43. That is,the silicone rubber which is of the cushioning material 306, is placedabout half around the surface inside the enduing unit 207 whileincluding a directly overhead portion of the ultrasonic detector 305.Additionally the gap between the cushioning material 306 and the frame311 is filled with the sound absorbing material 307.

The semiconductor laser device may be used as the light source chip 314which is of the light generating means. In addition to a compact sizeand a long lifetime, the semiconductor laser has an advantage that theintensity modulation operation necessary to the photoacoustic, methodcan directly be performed to the device by modulating the injectioncurrent.

When the semiconductor laser device is used as the light source chip314, usually the output beam 315 is a diffuse light flux, and the beamdiameter is much smaller than a beam diameter suitable to thephotoacoustic method immediately after the light is outputted.Therefore, after the beam diameter is enlarged, it is necessary toobtain the irradiation light 304 to the living body. In the firstexample, the optical system for enlarging the beam diameter includes thereflecting mirror 316 and the concave mirror 317. That is, thereflecting mirror 316 is placed at a distance of 1.2 mm from theoutgoing end face of the light source chip 314 with respect to theoutput beam 315 having the outgoing total angle of 46° (numericalaperture NA=0.39), and the output beam 315 is reflected toward theconcave mirror 317 located above. The concave mirror 317 is maintainedwhile separated away from the reflecting mirror 316 by 4.7 mm. Theconcave mirror 317 converts the incident light flux from the reflectingmirror 316 into the parallel light flux, and the concave mirror 317reflects the light toward the direction of the irradiation window 313(downward of FIG. 43).

In the first example, the focal distance, i.e., ½ of the radius ofcurvature of the concave mirror 317 is set so as to be equal to the sumof the optical path between the outgoing end face of the light sourcechip 314 and the reflecting mirror 316 and the optical path between thereflecting mirror 316 and the concave mirror 317, so that theirradiation light 304 having the diameter of 5.0 mm is obtained throughthe irradiation window 313.

The irradiation window 313 protects the light source chip 314, thereflecting mirror 316, and the concave mirror 317, and the irradiationwindow 313 also functions as a seat plate with which the light sourcechip 314 and the reflecting mirror 316 are attached with high accuracy.Because the transparency to the irradiation light 304 and the scratchresistance are required for the material for the irradiation window 313,the sapphire plate is used in the first embodiment.

The backside of the concave mirror 317 is a portion corresponding to thetop of the bezel of the ring in the enduing unit 207, and the backsideof the concave mirror 317 is the point which plays the central role inthe usual use as the ring of the jewelry. In the first example, thebackside of the concave mirror 317 can be utilized for the purpose ofornament.

It is necessary that the irradiation window 313 and the concave mirror317 be fixed to the frame 311 while the relative positions aremaintained. Therefore, a notch for alignment of the irradiation window313 and the concave mirror 317 is provided in the frame 311. The frame311 also includes a hollow portion (wiring cavity) for electric wiringand a groove to which the sound absorbing material 307 and thecushioning material 306 are bonded. Similarly to the ring base, theframe 311 having the above structure can sufficiently be generated by adie (casting) technique in the jewelry industry.

FIG. 44 shows a mounting mode of the light source chip 314. The twosemiconductor laser devices having the different wavelengths are used inthe first example. Specifically, the semiconductor laser device isformed on a substrate 321 shown in FIG. 44 by a MEMS technique. Thesubstantial size of the light source chip 314 shown in FIG. 44 is 1mm×1.5 mm×0.6 mm (thickness), and the light source chip 314 has the sizewhich can easily be mounted as the ring type enduing means.

In FIG. 44, the first semiconductor laser 318 is placed at the end faceof a principal branch of an optical waveguide 322 made of polyimidefluoride, and the first semiconductor laser 318 outputs the laseroscillation light to the principal branch of the optical waveguide 322.On the other hand, the second semiconductor laser 319 is placed at theend face of a side branch of the optical waveguide 322 made of polyimidefluoride, and the second semiconductor laser 319 outputs the laseroscillation light to the side branch of the optical waveguide 322. Thedrive currents are supplied to the two semiconductor laser devicesthrough the electrode pads 320 respectively.

A coupler 323 which is of the light outgoing means, is formed at a nodalpoint of the principal branch and the side branch of the opticalwaveguide 322. The coupler 323 is the gap where the polyimide fluorideis removed. Based on the multiple interference effect, so-called etaloneffect, the coupler 323 exhibits the transmission for the oscillationwavelength of the first semiconductor laser 318, and the coupler 323exhibits the reflection for the oscillation wavelength of the secondsemiconductor laser 319.

According to the above configuration, the output light beams having thedifferent wavelengths outputted from the two semiconductor laser deviceare multiplexed, the light beam propagates in the optical waveguide 322,and the output beam 315 is outputted from the end face at which thesemiconductor laser device of the optical waveguide 322 is not placed.

FIG. 45 shows the ring type enduing unit, and FIG. 45 is a sectionalview taken on line a-a of FIG. 42. In FIG. 45, the ultrasonic detector305 and surroundings thereof are shown in an enlarged manner. Thewell-known piezoelectric ultrasonic wave detection device such as PZTand PVDF (polyvinylidene fluoride) can be used as ultrasonic detector305. However, because PZT has the high acoustic impedance, it isnecessary to add an impedance matching layer. Although PVDF is anadvantageous to the acoustic impedance, PVDF has the low output voltage,i.e., the low sensitivity. In the first example, a MEMS type ultrasonicwave detection device generated by the MEMS technique is used instead ofPZT or PVDF.

In FIG. 45, an ultrasonic detector 305 is formed by a vibration membrane324 and a fixed electrode 325.

The cushioning material 306 for acoustic matching is in contact with thevibration membrane 324 in the ultrasonic detector 305. In the MEMS typeultrasonic detector 305, a flow passage is provided in order to releasethe backpressure on the side of the fixed electrode 325. The flowpassage is communicated with the atmospheric pressure through a thinhole made in the frame 311 at the back of the fixed electrode 325. Theultrasonic detector 305 detects the ultrasonic wave by the capacitancechange caused by the displacement of the vibration membrane 324 in aflat sheet capacitor formed by the vibration membrane 324 and the fixedelectrode 325. Accordingly, in addition to the impedance conversionfunction, a function of supplying a constant electric charge to the flatsheet capacitor of the ultrasonic detector 305 is added to thepreamplifier 312 connected to the ultrasonic detector 305.

The preamplifier 312 and the wiring cavity 326 are placed in the frame311. The wiring cavity 326 is used for the wiring to the connectioncable 310 shown in FIG. 43. The frame 311 is located behind the soundabsorbing material 307. This configuration can prevent the preamplifier312 and the wiring cavity 326 from reflecting the ultrasonic wave.

In FIG. 41, various ideas could be made for the devices, circuits, andconnection methods among these devices and circuits, which areincorporated in the ring type enduing unit 207 and display unit 221without departing from the spirit of the sixth embodiment. For example,an optical fiber (small bending radius is advisable in order to hold thestretching properties of the cable) is included in the connection cable,the light source chip 314 is placed in display unit 221, and only theoptical system for enlarging the beam can be left as the light outgoingmeans of the ring type enduing unit 207.

On the other hand, a battery is incorporated in the ring type enduingunit 207, and all the components concerning the portable typenoninvasive blood constituent concentration measuring apparatusincluding the drive power supply of the light source and the phasesensitive amplifier can be mounted on the ring type enduing unit 207. Inthis case, the wireless communication of the blood constituentconcentration measured value can also be performed between the ring typeenduing unit 207 and the display unit 221.

Second Example

FIG. 46 shows a configuration in which the blood constituentconcentration measuring apparatus according to the sixth embodiment isapplied to the human body and realized as a wrist-fitted bracelet typeenduing means.

FIG. 46 shows a state in which the blood constituent concentrationmeasuring apparatus according to the sixth embodiment is fitted to thewrist as the bracelet type enduing means. In the fitting mode in thewrist of the bracelet type enduing means of the blood constituentconcentration measuring apparatus shown in FIG. 46, a bracelet typedisplay unit 419 fitted in a living body 400, which is of the testsubject, has the configuration in which the wrist-watch type displayunit 221 and ring type enduing unit 207 which are described in the firstexample are integrated.

An ultrasonic detector which is of the acoustic wave detection means, isincorporated into a display unit 419, and the light generating means,the light modulation means, and the light outgoing means are alsoincorporated in to the display unit 419. The display device whichdisplays the measurement result of the blood constituent concentration,is provided outside the display unit 419, and at least one button fordirecting the measurement start is also provided. The functions added tothe display unit 419 are similar to the first example.

FIG. 47 shows a state in which the bracelet type enduing means isdetached from the wrist. The bracelet type enduing means includes adisplay unit 419, a wrist band 428, and light irradiation unit 421 whichis of the light outgoing means, and all the components are placed so asto surround the wrist. The bracelet type enduing means has an appearancesimilar to the usual wristwatch, but bracelet type enduing means differsfrom the wristwatch in the attachment method. That is, in the case ofthe usual wristwatch, a buckle and the like for attachment anddetachment are placed in overlapping portions of both side bands(referred to as wristwatch band in the wristwatch). On the contrary, inthe bracelet type enduing means, the light irradiation unit 421 isplaced. Accordingly, another type of an attachment and detachmentmechanism is required in the bracelet type enduing means.

In the second example, the bracelet type enduing means is provided witha sheet-belt-like attachment and detachment mechanism including aninsertion key 429, an opening 430, and an release button 431 as theattachment and detachment mechanism of the bracelet type enduing means.

In the second example, the ultrasonic detector which is of the acousticwave detection means, is embedded in the back cover of the display unit419. Similarly to the first example, PZT, PVDF, and MEMS type ultrasonicwave detection device can be used as the ultrasonic detector.

The cushioning materials 418 are placed in the ultrasonic detector andcontact surfaces which is in contact with the living body on the bothsides of the ultrasonic detector, and the inside of the cushioningmaterial 418 is filled with the sound absorbing material.

In the second example, the bracelet type enduing means is fitted suchthat the ultrasonic detector comes into contact with the dorsal side ofthe wrist while the light irradiation unit 421 comes into contact withthe palm side. Because there is irregularity formed by the tendons oflong palmer muscle, basilic veins, and the like on the palm side of thewrist, the ultrasonic detector hardly comes into close contact with theskin to obtain the good acoustic coupling on the palm side of the wrist.

FIG. 48 shows sectional view along the center line from the lightirradiation unit 421 toward the wrist band 428. FIG. 48 shows a sectionof the light irradiation unit 421 of the bracelet type the enduing meansshown in FIG. 47. Similarly to the first example, after the beamdiameter of the output beam 415 of the light source chip 414 which is ofa part of the light generating means, is enlarged, the irradiation light417 to the living body is obtained.

In the second example, the optical system for enlarging the beamdiameter is composed of a reflecting mirror 416 and a lens 432. That is,the reflecting mirror 416 is placed at a distance of 2.7 mm from theoutgoing end face of the light source chip 414 with respect to theoutput beam 415 having the outgoing total angle of 46° (numericalaperture NA=0.39), and the output beam 415 is reflected toward the lens432. The lens 432 is maintained while separated away from the reflectingmirror 416 by 3.2 mm. The lens 432 converts the incident light flux fromthe reflecting mirror 416 into the parallel light flux, and the lens 432irradiates the light toward the direction of the irradiation window 413(upward of FIG. 48).

In the second example, the focal distance of the lens 432 is set so asto be equal to the sum of the optical path between the outgoing end faceof the light source chip 414 and the reflecting mirror 416 and theoptical path between the reflecting mirror 416 and the lens 432, so thatthe irradiation light 417 having the diameter of 5.0 mm is obtainedthrough the irradiation window 413. The irradiation window 413 isprovided to protect the components inside the light irradiation unit421, and it is necessary that the irradiation window 413 is transparentto the irradiation light 417 and scratch resistant. The light sourcechip 414 and the reflecting mirror 416 are attached to the light sourceschassis 433 with high accuracy.

In addition to the above examples, the bracelet type enduing meansaccording to the sixth embodiment can be also applied to an armlet inwhich a brachium is fitted, an anklet in which an ankle is fitted, and achoker ring in which the neck is fitted (however, only the anklet andthe choker ring having the good contact property can be used) withoutdeparting from the spirits of the embodiments.

INDUSTRIAL APPLICABILITY

The liquid constituent concentration measuring apparatus and liquidconstituent concentration measuring apparatus controlling methodaccording to the embodiments can be applied to the field of measuringthe constituent concentration in the liquid, for example, the sugarmeasurement of the fruit.

The blood constituent concentration measuring apparatus and controlmethod of blood constituent concentration measuring apparatus accordingto the embodiments can be utilized for daily health control and beautycheck. The blood constituent concentration measuring apparatus andcontrol method of blood constituent concentration measuring apparatusaccording to the embodiments can also be utilized not only for thehealth control of the living body of the human, but also for the healthcontrol of the living body of the animal.

The invention claimed is:
 1. A constituent concentration measuringapparatus comprising: light generating means for generating light; lightmodulation means for electrically intensity-modulating the light at aconstant frequency; light outgoing means for outputting the intensitymodulated light toward a test subject; an acoustic wave generator thatoutputs an acoustic wave; acoustic wave detection means for detecting aphotoacoustic signal emitted from the test subject, which is irradiatedwith the intensity modulated light, as an actual signal, and fordetecting an intensity of the acoustic wave output by the acoustic wavegenerator and transmitted through the test subject as a referencesignal; drive means for varying a position of at least one of theacoustic wave generator, the light outgoing means, and the acoustic wavedetection means; and control means for controlling the drive means todetect plural reference signals from a plurality of positions, analyzingthe plurality of reference signals to determine an optimum propagationpath having minimized reflection/scattering characteristics, anddetecting the actual photoacoustic signal from the positioncorresponding with the optimum propagation path.
 2. The constituentconcentration measuring apparatus as claimed in claim 1, wherein thecontrol means is further configured for: subsequent to detecting theplurality of reference signals and determining the optimum propagationpath, controlling the drive means to position at least one of theacoustic wave generator, the light outgoing means, and the acoustic wavedetection means such that the photoacoustic signal emitted from the testsubject propagates in the optimum propagation path, and causing thelight outgoing means to irradiate the test subject with the intensitymodulated light for detecting the actual photoacoustic signal.
 3. Theconstituent concentration measuring apparatus as claimed in claim 1,wherein the control means is further configured for: in addition to thereference signal, detecting a photoacoustic signal for each of theplurality of positions; and selecting the photoacostic signalcorresponding with the optimum propagation path as the actualphotoacoustic signal.
 4. A constituent concentration measuring apparatusas claimed in claim 1, wherein the light outgoing means is fixed to theacoustic wave generator so as to keep a relative position to theacoustic wave generator.
 5. A constituent concentration measuringapparatus as claimed in claim 1, further comprising: pressing means forpressing the acoustic wave generator and the acoustic wave detectionmeans against the test subject with a pressing force whose pressure canbe controlled.
 6. A constituent concentration measuring apparatus asclaimed in claim 1, wherein the acoustic wave generator is placed inproximity of the intensity modulated light outputted from the lightoutgoing means.
 7. A constituent concentration measuring apparatus asclaimed in claim 1, wherein the acoustic wave generator comprises atransmission window that transmits the intensity modulated light.
 8. Aconstituent concentration measuring apparatus as claimed in claim 1,wherein the frequency and/or the intensity of the acoustic wave outputby the acoustic wave generator is variable.
 9. A constituentconcentration measuring apparatus as claimed in claim 1, furthercomprising: an acoustic coupling element on a surface of the acousticwave generator and/or the light outgoing means that is configured to bein contact with the test subject and that has an acoustic impedancesubstantially equal to that of the test subject.
 10. A constituentconcentration measuring apparatus as claimed in claim 1, wherein thelight outgoing means outputs two light beams set to two wavelengths suchthat an absorption difference exhibited by a constituent set as ameasuring object is larger than an absorption difference exhibited byother constituents.
 11. A constituent concentration measuring methodcomprising: outputting, from a light source, light that is intensitymodulated at a constant frequency toward a test subject; outputting,from an acoustic wave generator, an acoustic wave toward the testsubject; detecting, with an acoustic wave detector, a photoacousticsignal emitted from the test subject as an actual signal, and anintensity of the acoustic wave output by the acoustic wave generator andtransmitted through the test subject as a reference signal; varying aposition of at least one of the acoustic wave generator, the lightsource, and the acoustic wave detector to detect plural referencesignals from a plurality of positions; analyzing the plurality ofreference signals to determine an optimum propagation path havingminimized reflection/scattering characteristics; and detecting theactual photoacoustic signal from the position corresponding with theoptimum propagation path.
 12. The constituent concentration measuringmethod as claimed in claim 11, further comprising: subsequent todetecting the plurality of reference signals and determining the optimumpropagation path, moving at least one of the acoustic wave generator,the light source, and the acoustic wave detector such that thephotoacoustic signal emitted from the test subject propagates in theoptimum propagation path, and causing the light source to irradiate thetest subject with the intensity modulated light for detecting the actualphotoacoustic signal.
 13. The constituent concentration measuring methodas claimed in claim 11, further comprising: in addition to the referencesignal, detecting a photoacoustic signal for each of the plurality ofpositions; and selecting the photoacostic signal corresponding with theoptimum propagation path as the actual photoacoustic signal.
 14. Aconstituent concentration measuring method as claimed in claim 11,further comprising: fixing the light source to the acoustic wavegenerator so as to keep a relative position to the acoustic wavegenerator.
 15. A constituent concentration measuring method as claimedin claim 11, further comprising: pressing the acoustic wave generatorand the acoustic wave detector against the test subject with a pressingforce whose pressure can be controlled.
 16. A constituent concentrationmeasuring method as claimed in claim 11, further comprising: placing theacoustic wave generator in proximity of the intensity modulated lightoutputted from the light source.
 17. A constituent concentrationmeasuring method as claimed in claim 11, wherein a transmission windowthat transmits the intensity modulated light is formed in the acousticwave generator.
 18. A constituent concentration measuring method asclaimed in claim 11, wherein the frequency and/or the intensity of theacoustic wave is variable.
 19. A constituent concentration measuringmethod as claimed in claim 11, further comprising: providing an acousticcoupling element on a surface of the acoustic wave generator and/or thelight source that is configured to be in contact with the test subjectand that has an acoustic impedance substantially equal to that of thetest subject.
 20. A constituent concentration measuring apparatus asclaimed in claim 11, further comprising: outputting, from the lightsource, two light beams set to two wavelengths such that an absorptiondifference exhibited by a constituent set as a measuring object islarger than an absorption difference exhibited by other constituents.